5-141351482-C-A

Position:

chr5-141351482-C-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_018922.3(PCDHGB1):c.1222C>A(p.Arg408=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00645 in 1,613,848 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0055 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0065 ( 39 hom. )

Consequence

PCDHGB1
NM_018922.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.127

Variant links:

Genes affected

PCDHGB1 (HGNC:8708): (protocadherin gamma subfamily B, 1) This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

PCDHGB1 links:

PCDHGA1 (HGNC:8696): (protocadherin gamma subfamily A, 1) This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

PCDHGA1 links:

PCDHGA2 (HGNC:8700): (protocadherin gamma subfamily A, 2) This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

PCDHGA2 links:

PCDHGA3 (HGNC:8701): (protocadherin gamma subfamily A, 3) This gene is a member of the protocadherin gamma gene cluster, one of three related clusters tandemly linked on chromosome five. These gene clusters have an immunoglobulin-like organization, suggesting that a novel mechanism may be involved in their regulation and expression. The gamma gene cluster includes 22 genes divided into 3 subfamilies. Subfamily A contains 12 genes, subfamily B contains 7 genes and 2 pseudogenes, and the more distantly related subfamily C contains 3 genes. The tandem array of 22 large, variable region exons are followed by a constant region, containing 3 exons shared by all genes in the cluster. Each variable region exon encodes the extracellular region, which includes 6 cadherin ectodomains and a transmembrane region. The constant region exons encode the common cytoplasmic region. These neural cadherin-like cell adhesion proteins most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been described for the gamma cluster genes. [provided by RefSeq, Jul 2008]

PCDHGA3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 5-141351482-C-A is Benign according to our data. Variant chr5-141351482-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2655842.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.127 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCDHGB1	NM_018922.3 linkuse as main transcript	c.1222C>A	p.Arg408=	synonymous_variant	1/4	ENST00000523390.2
PCDHGA1	NM_018912.3 linkuse as main transcript	c.2421+18377C>A		intron_variant		ENST00000517417.3
PCDHGA2	NM_018915.4 linkuse as main transcript	c.2424+10087C>A		intron_variant		ENST00000394576.3
PCDHGA3	NM_018916.4 linkuse as main transcript	c.2424+5025C>A		intron_variant		ENST00000253812.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDHGB1	ENST00000523390.2 linkuse as main transcript	c.1222C>A	p.Arg408=	synonymous_variant	1/4	1	NM_018922.3	P1	Q9Y5G3-1
PCDHGA3	ENST00000253812.8 linkuse as main transcript	c.2424+5025C>A		intron_variant		1	NM_018916.4	P1	Q9Y5H0-1
PCDHGA2	ENST00000394576.3 linkuse as main transcript	c.2424+10087C>A		intron_variant		1	NM_018915.4	P1	Q9Y5H1-1
PCDHGA1	ENST00000517417.3 linkuse as main transcript	c.2421+18377C>A		intron_variant		1	NM_018912.3	P1	Q9Y5H4-1

Frequencies

GnomAD3 genomes

AF:

0.00552

AC:

840

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00477

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00648

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00653

AC:

1624

AN:

248792

Hom.:

AF XY:

0.00641

AC XY:

866

AN XY:

135002

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00147

Gnomad FIN exome

AF:

0.0259

Gnomad NFE exome

AF:

0.00769

Gnomad OTH exome

AF:

0.00711

GnomAD4 exome

AF:

0.00655

AC:

9569

AN:

1461528

Hom.:

Cov.:

AF XY:

0.00636

AC XY:

4627

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00269

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00134

Gnomad4 FIN exome

AF:

0.0260

Gnomad4 NFE exome

AF:

0.00683

Gnomad4 OTH exome

AF:

0.00502

GnomAD4 genome

AF:

0.00552

AC:

841

AN:

152320

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

458

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00483

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0240

Gnomad4 NFE

AF:

0.00648

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00521

Hom.:

Bravo

AF:

0.00384

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00529

EpiControl

AF:

0.00535

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

PCDHGB1: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

8.1

DANN

Benign

0.81

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over