rs2297815

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_015404.4(WHRN):c.117G>A(p.Val39Val) 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:8

Conservation

PhyloP100: 0.584

Publications

20 publications found

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 Gene-Disease associations (from GenCC):

Usher syndrome type 2D
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P
autosomal recessive nonsyndromic hearing loss 31
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
nonsyndromic genetic hearing loss
Inheritance: AR Classification: MODERATE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Usher syndrome type 2
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

WHRN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 45644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
WHRN	NM_015404.4 link	c.117G>A	p.Val39Val	synonymous_variant	Exon 1 of 12	ENST00000362057.4	NP_056219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4 link	c.117G>A	p.Val39Val	synonymous_variant	Exon 1 of 12	1	NM_015404.4	ENSP00000354623.3

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

GnomAD2 exomes

AF:

0.326

AC:

69865

AN:

214404

AF XY:

0.325

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 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

African (AFR)

AF:

0.227

AC:

7493

AN:

32980

American (AMR)

AF:

0.326

AC:

14211

AN:

43582

Ashkenazi Jewish (ASJ)

AF:

0.354

AC:

8967

AN:

25366

East Asian (EAS)

AF:

0.172

AC:

6757

AN:

39248

South Asian (SAS)

AF:

0.226

AC:

19117

AN:

84554

European-Finnish (FIN)

AF:

0.487

AC:

21559

AN:

44252

Middle Eastern (MID)

AF:

0.305

AC:

1591

AN:

5220

European-Non Finnish (NFE)

AF:

0.370

AC:

409326

AN:

1105912

Other (OTH)

AF:

0.326

AC:

19412

AN:

59612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

20914

41828

62741

83655

104569

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12828

25656

38484

51312

64140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.326

AC:

49587

AN:

152154

Hom.:

8605

Cov.:

AF XY:

0.329

AC XY:

24498

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.236

AC:

9795

AN:

41540

American (AMR)

AF:

0.336

AC:

5139

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1193

AN:

3470

East Asian (EAS)

AF:

0.139

AC:

717

AN:

5164

South Asian (SAS)

AF:

0.220

AC:

1062

AN:

4834

European-Finnish (FIN)

AF:

0.507

AC:

5363

AN:

10578

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.372

AC:

25248

AN:

67956

Other (OTH)

AF:

0.321

AC:

678

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1763

3526

5290

7053

8816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

496

992

1488

1984

2480

<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:

0.339

Hom.:

3641

Bravo

AF:

0.308

Asia WGS

AF:

0.204

AC:

713

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Jun 12, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 26, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 31

Benign:2

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.58

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over