Variant chr9-114424312-T-A 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_015404.4(WHRN):c.1416+22A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,610,756 control chromosomes in the GnomAD database, including 47,016 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3678 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43338 hom. )

Consequence

WHRN
NM_015404.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.645

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=-0.86).

BP6

Variant 9-114424312-T-A is Benign according to our data. Variant chr9-114424312-T-A is described in ClinVar as [Benign]. Clinvar id is 1230190.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-114424312-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.315 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.1416+22A>T		intron_variant		ENST00000362057.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WHRN	ENST00000362057.4 linkuse as main transcript	c.1416+22A>T		intron_variant		1	NM_015404.4	P1	Q9P202-1

Frequencies

GnomAD3 genomes

AF:

0.202

AC:

30636

AN:

151904

Hom.:

3666

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0732

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.301

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.328

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.276

Gnomad MID

AF:

0.204

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.222

GnomAD3 exomes

AF:

0.264

AC:

66122

AN:

250498

Hom.:

9918

AF XY:

0.259

AC XY:

35133

AN XY:

135480

show subpopulations

Gnomad AFR exome

AF:

0.0696

Gnomad AMR exome

AF:

0.431

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.330

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.272

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.244

GnomAD4 exome

AF:

0.237

AC:

345359

AN:

1458730

Hom.:

43338

Cov.:

AF XY:

0.237

AC XY:

172334

AN XY:

725726

show subpopulations

Gnomad4 AFR exome

AF:

0.0634

Gnomad4 AMR exome

AF:

0.416

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.359

Gnomad4 SAS exome

AF:

0.275

Gnomad4 FIN exome

AF:

0.269

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.202

AC:

30667

AN:

152026

Hom.:

3678

Cov.:

AF XY:

0.205

AC XY:

15224

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0731

Gnomad4 AMR

AF:

0.301

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.328

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.276

Gnomad4 NFE

AF:

0.229

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.211

Hom.:

667

Bravo

AF:

0.200

Asia WGS

AF:

0.247

AC:

859

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Autosomal recessive nonsyndromic hearing loss 31

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.8

DANN

Benign

0.69

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