Variant 9-114426434-T-C 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.964-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 1,612,952 control chromosomes in the GnomAD database, including 74,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7470 hom., cov: 33)

Exomes 𝑓: 0.30 ( 67272 hom. )

Consequence

WHRN
NM_015404.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.643

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:

WHRN (HGNC:):

WHRN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-114426434-T-C is Benign according to our data. Variant chr9-114426434-T-C is described in ClinVar as [Benign]. Clinvar id is 1238923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-114426434-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WHRN	NM_015404.4 linkuse as main transcript	c.964-21A>G		intron_variant		ENST00000362057.4	NP_056219.3	Q9P202-1B9EGE6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4 linkuse as main transcript	c.964-21A>G		intron_variant		1	NM_015404.4	ENSP00000354623.3		Q9P202-1

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

47540

AN:

151868

Hom.:

7449

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.373

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.286

Gnomad OTH

AF:

0.320

GnomAD3 exomes

AF:

0.330

AC:

81254

AN:

246114

Hom.:

14068

AF XY:

0.323

AC XY:

43129

AN XY:

133414

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.468

Gnomad ASJ exome

AF:

0.282

Gnomad EAS exome

AF:

0.384

Gnomad SAS exome

AF:

0.350

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.286

Gnomad OTH exome

AF:

0.305

GnomAD4 exome

AF:

0.300

AC:

438246

AN:

1460966

Hom.:

67272

Cov.:

AF XY:

0.300

AC XY:

218253

AN XY:

726756

show subpopulations

Gnomad4 AFR exome

AF:

0.332

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.352

Gnomad4 FIN exome

AF:

0.286

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.304

GnomAD4 genome

AF:

0.313

AC:

47611

AN:

151986

Hom.:

7470

Cov.:

AF XY:

0.313

AC XY:

23281

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.374

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.286

Gnomad4 OTH

AF:

0.317

Alfa

AF:

0.308

Hom.:

3584

Bravo

AF:

0.323

Asia WGS

AF:

0.332

AC:

1155

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.91

CADD

Benign

8.8

DANN

Benign

0.76

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