9-114403926-G-T

Variant names:

Variant summary

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

The NM_015404.4(WHRN):c.2388C>A(p.Asn796Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,610,268 control chromosomes in the GnomAD database, including 45,475 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3552 hom., cov: 32)

Exomes 𝑓: 0.23 ( 41923 hom. )

Consequence

WHRN
NM_015404.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -3.21

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041309297).

BP6

Variant 9-114403926-G-T is Benign according to our data. Variant chr9-114403926-G-T is described in ClinVar as [Benign]. Clinvar id is 45674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-114403926-G-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.316 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WHRN	NM_015404.4 link	c.2388C>A	p.Asn796Lys	missense_variant	Exon 10 of 12	ENST00000362057.4	NP_056219.3	Q9P202-1B9EGE6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4 link	c.2388C>A	p.Asn796Lys	missense_variant	Exon 10 of 12	1	NM_015404.4	ENSP00000354623.3		Q9P202-1

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30360

AN:

151914

Hom.:

3546

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0740

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.277

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.255

AC:

63508

AN:

249462

Hom.:

8864

AF XY:

0.252

AC XY:

34053

AN XY:

134980

show subpopulations

Gnomad AFR exome

AF:

0.0714

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.236

Gnomad EAS exome

AF:

0.334

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.237

GnomAD4 exome

AF:

0.234

AC:

341502

AN:

1458234

Hom.:

41923

Cov.:

AF XY:

0.235

AC XY:

170635

AN XY:

725572

show subpopulations

Gnomad4 AFR exome

AF:

0.0650

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.360

Gnomad4 SAS exome

AF:

0.268

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.227

GnomAD4 genome

AF:

0.200

AC:

30380

AN:

152034

Hom.:

3552

Cov.:

AF XY:

0.203

AC XY:

15118

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0739

Gnomad4 AMR

AF:

0.277

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.329

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.220

Hom.:

9181

Bravo

AF:

0.195

TwinsUK

AF:

0.227

AC:

842

ALSPAC

AF:

0.248

AC:

955

ESP6500AA

AF:

0.0801

AC:

353

ESP6500EA

AF:

0.231

AC:

1987

ExAC

AF:

0.247

AC:

30044

Asia WGS

AF:

0.245

AC:

850

AN:

3478

EpiCase

AF:

0.226

EpiControl

AF:

0.222

ClinVar

Significance: Benign

Submissions summary: Benign:9

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

Jun 19, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal recessive nonsyndromic hearing loss 31

Benign:2

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. -

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa-deafness syndrome

Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.0010

DANN

Benign

0.66

DEOGEN2

Benign

0.076

.;.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.6

.;.;L

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.52

N;N;N

REVEL

Benign

0.0050

Sift

Benign

0.32

T;T;T

Sift4G

Benign

0.77

T;T;T

Polyphen

0.023, 0.013

.;B;B

Vest4

0.12

MutPred

0.36

.;.;Gain of methylation at N796 (P = 0.0091);

MPC

0.14

ClinPred

0.0055

GERP RS

-7.5

Varity_R

0.045

gMVP

0.16

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