9-114426193-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015404.4(WHRN):c.1166+18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00572 in 1,611,748 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0059 ( 35 hom. )

Consequence

WHRN
NM_015404.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.72

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 (BayesDel_noAF=-0.87).

BP6

Variant 9-114426193-C-T is Benign according to our data. Variant chr9-114426193-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 137079.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-114426193-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00432 (658/152232) while in subpopulation NFE AF= 0.00731 (497/68008). AF 95% confidence interval is 0.00678. There are 2 homozygotes in gnomad4. There are 287 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WHRN	NM_015404.4 link	c.1166+18G>A		intron_variant	Intron 4 of 11	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.1166+18G>A		intron_variant	Intron 4 of 11	1	NM_015404.4	ENSP00000354623.3		Q9P202-1

Frequencies

GnomAD3 genomes

AF:

0.00433

AC:

658

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00575

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00731

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00467

AC:

1171

AN:

250518

Hom.:

AF XY:

0.00478

AC XY:

647

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00983

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00248

Gnomad FIN exome

AF:

0.00735

Gnomad NFE exome

AF:

0.00665

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00587

AC:

8565

AN:

1459516

Hom.:

Cov.:

AF XY:

0.00589

AC XY:

4274

AN XY:

726044

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00260

Gnomad4 FIN exome

AF:

0.00717

Gnomad4 NFE exome

AF:

0.00652

Gnomad4 OTH exome

AF:

0.00545

GnomAD4 genome

AF:

0.00432

AC:

658

AN:

152232

Hom.:

Cov.:

AF XY:

0.00386

AC XY:

287

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00104

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00575

Gnomad4 NFE

AF:

0.00731

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00584

Hom.:

Bravo

AF:

0.00377

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Mar 19, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Sep 08, 2021

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 2D;C1846839:Autosomal recessive nonsyndromic hearing loss 31

Benign:1

Jan 07, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely 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

-0.87

CADD

Benign

0.0030

DANN

Benign

0.61

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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