rs3812658

Positions:

chr10-54020155-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_033056.4(PCDH15):c.2751+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,578,954 control chromosomes in the GnomAD database, including 390,397 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 29492 hom., cov: 31)

Exomes 𝑓: 0.70 ( 360905 hom. )

Consequence

PCDH15
NM_033056.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.118

Variant links:

Genes affected

PCDH15 (HGNC:14674): (protocadherin related 15) This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. It plays an essential role in maintenance of normal retinal and cochlear function. Mutations in this gene result in hearing loss and Usher Syndrome Type IF (USH1F). Extensive alternative splicing resulting in multiple isoforms has been observed in the mouse ortholog. Similar alternatively spliced transcripts are inferred to occur in human, and additional variants are likely to occur. [provided by RefSeq, Dec 2008]

PCDH15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 10-54020155-G-A is Benign according to our data. Variant chr10-54020155-G-A is described in ClinVar as [Benign]. Clinvar id is 262147.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-54020155-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCDH15	NM_001384140.1 linkuse as main transcript	c.2751+37C>T		intron_variant		ENST00000644397.2
PCDH15	NM_033056.4 linkuse as main transcript	c.2751+37C>T		intron_variant		ENST00000320301.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCDH15	ENST00000320301.11 linkuse as main transcript	c.2751+37C>T		intron_variant		1	NM_033056.4		Q96QU1-1
PCDH15	ENST00000644397.2 linkuse as main transcript	c.2751+37C>T		intron_variant			NM_001384140.1

Frequencies

GnomAD3 genomes

AF:

0.593

AC:

89924

AN:

151724

Hom.:

29489

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.667

Gnomad AMR

AF:

0.702

Gnomad ASJ

AF:

0.736

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.463

Gnomad FIN

AF:

0.690

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.742

Gnomad OTH

AF:

0.642

GnomAD3 exomes

AF:

0.647

AC:

160334

AN:

247826

Hom.:

54923

AF XY:

0.646

AC XY:

86521

AN XY:

134034

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.745

Gnomad ASJ exome

AF:

0.740

Gnomad EAS exome

AF:

0.336

Gnomad SAS exome

AF:

0.475

Gnomad FIN exome

AF:

0.689

Gnomad NFE exome

AF:

0.744

Gnomad OTH exome

AF:

0.711

GnomAD4 exome

AF:

0.701

AC:

1000658

AN:

1427112

Hom.:

360905

Cov.:

AF XY:

0.696

AC XY:

495701

AN XY:

712210

show subpopulations

Gnomad4 AFR exome

AF:

0.305

Gnomad4 AMR exome

AF:

0.741

Gnomad4 ASJ exome

AF:

0.744

Gnomad4 EAS exome

AF:

0.275

Gnomad4 SAS exome

AF:

0.483

Gnomad4 FIN exome

AF:

0.692

Gnomad4 NFE exome

AF:

0.745

Gnomad4 OTH exome

AF:

0.675

GnomAD4 genome

AF:

0.592

AC:

89935

AN:

151842

Hom.:

29492

Cov.:

AF XY:

0.589

AC XY:

43672

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.702

Gnomad4 ASJ

AF:

0.736

Gnomad4 EAS

AF:

0.292

Gnomad4 SAS

AF:

0.463

Gnomad4 FIN

AF:

0.690

Gnomad4 NFE

AF:

0.742

Gnomad4 OTH

AF:

0.636

Alfa

AF:

0.718

Hom.:

39033

Bravo

AF:

0.587

Asia WGS

AF:

0.361

AC:

1255

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Autosomal recessive nonsyndromic hearing loss 23

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Usher syndrome type 1F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.30

DANN

Benign

0.19

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