Variant rs11594958 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 NM_001384140.1(PCDH15):c.319-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,602,738 control chromosomes in the GnomAD database, including 30,982 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3151 hom., cov: 32)

Exomes 𝑓: 0.19 ( 27831 hom. )

Consequence

PCDH15
NM_001384140.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.649

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-54369306-A-G is Benign according to our data. Variant chr10-54369306-A-G is described in ClinVar as [Benign]. Clinvar id is 262150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-54369306-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCDH15	NM_033056.4 linkuse as main transcript	c.319-31T>C		intron_variant		ENST00000320301.11	NP_149045.3	Q96QU1-1
PCDH15	NM_001384140.1 linkuse as main transcript	c.319-31T>C		intron_variant		ENST00000644397.2	NP_001371069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCDH15	ENST00000320301.11 linkuse as main transcript	c.319-31T>C		intron_variant		1	NM_033056.4	ENSP00000322604.6		Q96QU1-1
PCDH15	ENST00000644397.2 linkuse as main transcript	c.319-31T>C		intron_variant			NM_001384140.1	ENSP00000495195.1		A0A2R8Y6C0

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30621

AN:

151904

Hom.:

3145

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.233

Gnomad ASJ

AF:

0.192

Gnomad EAS

AF:

0.0927

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.196

Gnomad OTH

AF:

0.213

GnomAD3 exomes

AF:

0.198

AC:

47796

AN:

241600

Hom.:

4804

AF XY:

0.198

AC XY:

25901

AN XY:

130636

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.239

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.0944

Gnomad SAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.162

Gnomad NFE exome

AF:

0.200

Gnomad OTH exome

AF:

0.206

GnomAD4 exome

AF:

0.193

AC:

280495

AN:

1450716

Hom.:

27831

Cov.:

AF XY:

0.194

AC XY:

139910

AN XY:

721660

show subpopulations

Gnomad4 AFR exome

AF:

0.228

Gnomad4 AMR exome

AF:

0.241

Gnomad4 ASJ exome

AF:

0.186

Gnomad4 EAS exome

AF:

0.0661

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.158

Gnomad4 NFE exome

AF:

0.195

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.202

AC:

30640

AN:

152022

Hom.:

3151

Cov.:

AF XY:

0.199

AC XY:

14776

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.233

Gnomad4 ASJ

AF:

0.192

Gnomad4 EAS

AF:

0.0927

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.196

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.200

Hom.:

595

Bravo

AF:

0.210

Asia WGS

AF:

0.149

AC:

517

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Usher syndrome type 1F

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.2

DANN

Benign

0.48

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