dbSNP rs17642669: PCDHB15:c.*767A>G (chr5-141248709-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_018935.4(PCDHB15):c.*767A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,188 control chromosomes in the GnomAD database, including 177 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 0.046 ( 177 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCDHB15
NM_018935.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.124

Publications

2 publications found

Variant links:

Genes affected

PCDHB15 (HGNC:8686): (protocadherin beta 15) This gene is a member of the protocadherin beta gene cluster, one of three related gene clusters tandemly linked on chromosome five. The gene clusters demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The beta cluster contains 16 genes and 3 pseudogenes, each encoding 6 extracellular cadherin domains and a cytoplasmic tail that deviates from others in the cadherin superfamily. The extracellular domains interact in a homophilic manner to specify differential cell-cell connections. Unlike the alpha and gamma clusters, the transcripts from these genes are made up of only one large exon, not sharing common 3' exons as expected. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins. Their specific functions are unknown but they most likely play a critical role in the establishment and function of specific cell-cell neural connections. [provided by RefSeq, Jul 2008]

PCDHB15 links:

PCDHB@ (HGNC:8679):

PCDHB@ links:

ENSG00000280029 (HGNC:):

ENSG00000280029 links:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCDHB15	NM_018935.4 link	c.*767A>G		3_prime_UTR_variant	Exon 1 of 1	ENST00000231173.6	NP_061758.1	Q9Y5E8B2R708
PCDHB@		n.141248709A>G		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCDHB15	ENST00000231173.6 link	c.*767A>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_018935.4	ENSP00000231173.3		Q9Y5E8
ENSG00000280029	ENST00000726815.1 link	n.125-856T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0459

AC:

6982

AN:

152070

Hom.:

177

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0327

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0392

Gnomad ASJ

AF:

0.0571

Gnomad EAS

AF:

0.000581

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0578

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0582

Gnomad OTH

AF:

0.0445

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0459

AC:

6986

AN:

152188

Hom.:

177

Cov.:

AF XY:

0.0447

AC XY:

3325

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0327

AC:

1357

AN:

41522

American (AMR)

AF:

0.0391

AC:

597

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0571

AC:

198

AN:

3466

East Asian (EAS)

AF:

0.000582

AC:

AN:

5154

South Asian (SAS)

AF:

0.0174

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0578

AC:

612

AN:

10596

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0583

AC:

3962

AN:

68014

Other (OTH)

AF:

0.0440

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

338

677

1015

1354

1692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0505

Hom.:

245

Bravo

AF:

0.0433

Asia WGS

AF:

0.00924

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.2

(source)

DANN

Benign

0.38

PhyloP100

0.12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over