rs2297815

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_015404.4(WHRN):c.117G>A(p.Val39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,592,880 control chromosomes in the GnomAD database, including 100,676 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8605 hom., cov: 34)

Exomes 𝑓: 0.35 ( 92071 hom. )

Consequence

WHRN
NM_015404.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.584

Variant links:

Genes affected

WHRN (HGNC:16361): (whirlin) This gene is thought to function in the organization and stabilization of sterocilia elongation and actin cystoskeletal assembly, based on studies of the related mouse gene. Mutations in this gene have been associated with autosomal recessive non-syndromic deafness and Usher Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

WHRN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 9-114504685-C-T is Benign according to our data. Variant chr9-114504685-C-T is described in ClinVar as [Benign]. Clinvar id is 45644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-114504685-C-T is described in Lovd as [Likely_benign]. Variant chr9-114504685-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WHRN	NM_015404.4 linkuse as main transcript	c.117G>A	p.Val39=	synonymous_variant	1/12	ENST00000362057.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WHRN	ENST00000362057.4 linkuse as main transcript	c.117G>A	p.Val39=	synonymous_variant	1/12	1	NM_015404.4	P1	Q9P202-1
WHRN	ENST00000374057.3 linkuse as main transcript	c.117G>A	p.Val39=	synonymous_variant	1/2	2			Q9P202-2

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49598

AN:

152038

Hom.:

8609

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.338

Gnomad AMR

AF:

0.336

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.507

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.372

Gnomad OTH

AF:

0.325

GnomAD3 exomes

AF:

0.326

AC:

69865

AN:

214404

Hom.:

11896

AF XY:

0.325

AC XY:

38523

AN XY:

118696

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.330

Gnomad ASJ exome

AF:

0.359

Gnomad EAS exome

AF:

0.141

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.494

Gnomad NFE exome

AF:

0.371

Gnomad OTH exome

AF:

0.355

GnomAD4 exome

AF:

0.353

AC:

508433

AN:

1440726

Hom.:

92071

Cov.:

AF XY:

0.350

AC XY:

250231

AN XY:

715960

show subpopulations

Gnomad4 AFR exome

AF:

0.227

Gnomad4 AMR exome

AF:

0.326

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.226

Gnomad4 FIN exome

AF:

0.487

Gnomad4 NFE exome

AF:

0.370

Gnomad4 OTH exome

AF:

0.326

GnomAD4 genome

AF:

0.326

AC:

49587

AN:

152154

Hom.:

8605

Cov.:

AF XY:

0.329

AC XY:

24498

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.336

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.139

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.507

Gnomad4 NFE

AF:

0.372

Gnomad4 OTH

AF:

0.321

Alfa

AF:

0.356

Hom.:

2225

Bravo

AF:

0.308

Asia WGS

AF:

0.204

AC:

713

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 12, 2009	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 26, 2014	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Autosomal recessive nonsyndromic hearing loss 31

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Usher syndrome type 2D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Benign

0.96

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