Variant rs16937769 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000395445.6(PCDH15):c.4602A>C(p.Thr1534=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,614,020 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 46 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 102 hom. )

Consequence

PCDH15
ENST00000395445.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.41

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=-0.81).

BP6

Variant 10-53809442-T-G is Benign according to our data. Variant chr10-53809442-T-G is described in ClinVar as [Benign]. Clinvar id is 44033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_001384140.1 linkuse as main transcript	c.4671+1114A>C		intron_variant		ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000644397.2 linkuse as main transcript	c.4671+1114A>C		intron_variant			NM_001384140.1	ENSP00000495195

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1786

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0599

Gnomad SAS

AF:

0.0128

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00867

AC:

2156

AN:

248800

Hom.:

AF XY:

0.00797

AC XY:

1078

AN XY:

135184

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.00319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0615

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.00195

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.00843

GnomAD4 exome

AF:

0.00344

AC:

5035

AN:

1461694

Hom.:

102

Cov.:

AF XY:

0.00347

AC XY:

2521

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.0293

Gnomad4 AMR exome

AF:

0.00315

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0568

Gnomad4 SAS exome

AF:

0.0109

Gnomad4 FIN exome

AF:

0.00157

Gnomad4 NFE exome

AF:

0.000147

Gnomad4 OTH exome

AF:

0.00765

GnomAD4 genome

AF:

0.0118

AC:

1790

AN:

152326

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

885

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0308

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0601

Gnomad4 SAS

AF:

0.0128

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.00327

Hom.:

Bravo

AF:

0.0128

Asia WGS

AF:

0.0570

AC:

196

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 23, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 23, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Sep 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 07, 2012

Thr1541Thr in Exon 36 of PCDH15: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 3.2% (77/2374) of African American chromosomes from a broad population by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS; dbSNP rs16937769). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.052

DANN

Benign

0.47

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