rs59479

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_018900.4(PCDHA1):c.2394+93408A>C variant causes a intron change. The variant allele was found at a frequency of 0.658 in 1,137,016 control chromosomes in the GnomAD database, including 247,467 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.67 ( 33867 hom., cov: 33)

Exomes 𝑓: 0.66 ( 213600 hom. )

Consequence

PCDHA1
NM_018900.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.00

Variant links:

Genes affected

PCDHA1 (HGNC:8663): (protocadherin alpha 1) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA1 links:

PCDHA3 (HGNC:8669): (protocadherin alpha 3) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA3 links:

PCDHA6 (HGNC:8672): (protocadherin alpha 6) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA6 links:

PCDHA8 (HGNC:8674): (protocadherin alpha 8) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA8 links:

PCDHA9 (HGNC:8675): (protocadherin alpha 9) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA9 links:

PCDHA11 (HGNC:8665): (protocadherin alpha 11) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA11 links:

PCDHA10 (HGNC:8664): (protocadherin alpha 10) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA10 links:

PCDHA2 (HGNC:8668): (protocadherin alpha 2) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA2 links:

PCDHA4 (HGNC:8670): (protocadherin alpha 4) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA4 links:

PCDHA12 (HGNC:8666): (protocadherin alpha 12) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA12 links:

PCDHA7 (HGNC:8673): (protocadherin alpha 7) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA7 links:

PCDHA5 (HGNC:8671): (protocadherin alpha 5) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA5 links:

ENSG00000278901 (HGNC:):

ENSG00000278901 links:

PCDHA@ (HGNC:8662):

PCDHA@ links:

PCDHA13 (HGNC:8667): (protocadherin alpha 13) This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome five that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined. [provided by RefSeq, Jul 2008]

PCDHA13 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PCDHA1	NM_018900.4 link	c.2394+93408A>C	intron_variant	Intron 1 of 3	ENST00000504120.4	NP_061723.1	Q9Y5I3-1
PCDHA3	NM_018906.3 link	c.2394+78501A>C	intron_variant	Intron 1 of 3	ENST00000522353.3	NP_061729.1	Q9Y5H8-1
PCDHA6	NM_018909.4 link	c.2394+51607A>C	intron_variant	Intron 1 of 3	ENST00000529310.6	NP_061732.1	Q9UN73-1
PCDHA8	NM_018911.3 link	c.2394+38377A>C	intron_variant	Intron 1 of 3	ENST00000531613.2	NP_061734.1	Q9Y5H6-1
PCDHA9	NM_031857.2 link	c.2394+31203A>C	intron_variant	Intron 1 of 3	ENST00000532602.2	NP_114063.1	Q9Y5H5-1
PCDHA11	NM_018902.5 link	c.2391+10598A>C	intron_variant	Intron 1 of 3	ENST00000398640.7	NP_061725.1	Q9Y5I1-1
PCDHA10	NM_018901.4 link	c.2388+23656A>C	intron_variant	Intron 1 of 3	ENST00000307360.6	NP_061724.1	Q9Y5I2-1
PCDHA2	NM_018905.3 link	c.2388+84740A>C	intron_variant	Intron 1 of 3	ENST00000526136.2	NP_061728.1	Q9Y5H9-1
PCDHA4	NM_018907.4 link	c.2385+72520A>C	intron_variant	Intron 1 of 3	ENST00000530339.2	NP_061730.1	Q9UN74-1Q59H34
PCDHA12	NM_018903.4 link	c.2367+4253A>C	intron_variant	Intron 1 of 3	ENST00000398631.3	NP_061726.1	Q9UN75-1
PCDHA7	NM_018910.3 link	c.2355+45354A>C	intron_variant	Intron 1 of 3	ENST00000525929.2	NP_061733.1	Q9UN72-1
PCDHA5	NM_018908.3 link	c.2352+57965A>C	intron_variant	Intron 1 of 3	ENST00000529859.2	NP_061731.1	Q9Y5H7-1
PCDHA13	NM_018904.3 link	c.-177A>C	upstream_gene_variant		ENST00000289272.3	NP_061727.1	Q9Y5I0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PCDHA1	ENST00000504120.4 link	c.2394+93408A>C	intron_variant	Intron 1 of 3	1	NM_018900.4	ENSP00000420840.3	Q9Y5I3-1
PCDHA3	ENST00000522353.3 link	c.2394+78501A>C	intron_variant	Intron 1 of 3	1	NM_018906.3	ENSP00000429808.2	Q9Y5H8-1
PCDHA6	ENST00000529310.6 link	c.2394+51607A>C	intron_variant	Intron 1 of 3	1	NM_018909.4	ENSP00000433378.1	Q9UN73-1
PCDHA8	ENST00000531613.2 link	c.2394+38377A>C	intron_variant	Intron 1 of 3	1	NM_018911.3	ENSP00000434655.1	Q9Y5H6-1
PCDHA9	ENST00000532602.2 link	c.2394+31203A>C	intron_variant	Intron 1 of 3	1	NM_031857.2	ENSP00000436042.2	Q9Y5H5-1
PCDHA11	ENST00000398640.7 link	c.2391+10598A>C	intron_variant	Intron 1 of 3	1	NM_018902.5	ENSP00000381636.3	Q9Y5I1-1
PCDHA10	ENST00000307360.6 link	c.2388+23656A>C	intron_variant	Intron 1 of 3	1	NM_018901.4	ENSP00000304234.5	Q9Y5I2-1
PCDHA2	ENST00000526136.2 link	c.2388+84740A>C	intron_variant	Intron 1 of 3	1	NM_018905.3	ENSP00000431748.1	Q9Y5H9-1
PCDHA4	ENST00000530339.2 link	c.2385+72520A>C	intron_variant	Intron 1 of 3	1	NM_018907.4	ENSP00000435300.1	Q9UN74-1
PCDHA12	ENST00000398631.3 link	c.2367+4253A>C	intron_variant	Intron 1 of 3	1	NM_018903.4	ENSP00000381628.2	Q9UN75-1
PCDHA7	ENST00000525929.2 link	c.2355+45354A>C	intron_variant	Intron 1 of 3	1	NM_018910.3	ENSP00000436426.1	Q9UN72-1
PCDHA5	ENST00000529859.2 link	c.2352+57965A>C	intron_variant	Intron 1 of 3	1	NM_018908.3	ENSP00000436557.1	Q9Y5H7-1
PCDHA13	ENST00000289272.3 link	c.-177A>C	upstream_gene_variant		1	NM_018904.3	ENSP00000289272.2	Q9Y5I0-1

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

101113

AN:

152000

Hom.:

33823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.698

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.648

Gnomad ASJ

AF:

0.660

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.656

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.665

Gnomad OTH

AF:

0.664

GnomAD4 exome

AF:

0.657

AC:

647124

AN:

984898

Hom.:

213600

Cov.:

AF XY:

0.657

AC XY:

321900

AN XY:

490148

show subpopulations

Gnomad4 AFR exome

AF:

0.703

AC:

16048

AN:

22838

Gnomad4 AMR exome

AF:

0.610

AC:

13110

AN:

21482

Gnomad4 ASJ exome

AF:

0.668

AC:

11463

AN:

17168

Gnomad4 EAS exome

AF:

0.502

AC:

17622

AN:

35074

Gnomad4 SAS exome

AF:

0.648

AC:

36553

AN:

56388

Gnomad4 FIN exome

AF:

0.692

AC:

26207

AN:

37856

Gnomad4 NFE exome

AF:

0.663

AC:

495564

AN:

747542

Gnomad4 Remaining exome

AF:

0.654

AC:

28518

AN:

43600

Heterozygous variant carriers

10959

21918

32876

43835

54794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

11880

23760

35640

47520

59400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.665

AC:

101210

AN:

152118

Hom.:

33867

Cov.:

AF XY:

0.664

AC XY:

49362

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.698

AC:

0.698289

AN:

0.698289

Gnomad4 AMR

AF:

0.648

AC:

0.647659

AN:

0.647659

Gnomad4 ASJ

AF:

0.660

AC:

0.660426

AN:

0.660426

Gnomad4 EAS

AF:

0.473

AC:

0.472931

AN:

0.472931

Gnomad4 SAS

AF:

0.657

AC:

0.657415

AN:

0.657415

Gnomad4 FIN

AF:

0.692

AC:

0.691675

AN:

0.691675

Gnomad4 NFE

AF:

0.665

AC:

0.665122

AN:

0.665122

Gnomad4 OTH

AF:

0.665

AC:

0.664617

AN:

0.664617

Heterozygous variant carriers

1775

3549

5324

7098

8873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

806

1612

2418

3224

4030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.647

Hom.:

14206

Bravo

AF:

0.657

Asia WGS

AF:

0.630

AC:

2192

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.76

Mutation Taster

=100/0

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over