Variant 9-114403754-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000362057.4(WHRN):c.2418+142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,069,302 control chromosomes in the GnomAD database, including 123,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.41 ( 14100 hom., cov: 33)

Exomes 𝑓: 0.48 ( 109515 hom. )

Consequence

WHRN
ENST00000362057.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.657

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 9-114403754-T-C is Benign according to our data. Variant chr9-114403754-T-C is described in ClinVar as [Benign]. Clinvar id is 678779.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-114403754-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.501 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.2418+142A>G		intron_variant		ENST00000362057.4	NP_056219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4 linkuse as main transcript	c.2418+142A>G		intron_variant		1	NM_015404.4	ENSP00000354623	P1	Q9P202-1

Frequencies

GnomAD3 genomes

AF:

0.414

AC:

62975

AN:

151998

Hom.:

14093

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.501

Gnomad AMR

AF:

0.449

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.516

Gnomad FIN

AF:

0.479

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.491

Gnomad OTH

AF:

0.450

GnomAD4 exome

AF:

0.485

AC:

444472

AN:

917184

Hom.:

109515

AF XY:

0.489

AC XY:

232986

AN XY:

476834

show subpopulations

Gnomad4 AFR exome

AF:

0.211

Gnomad4 AMR exome

AF:

0.485

Gnomad4 ASJ exome

AF:

0.592

Gnomad4 EAS exome

AF:

0.505

Gnomad4 SAS exome

AF:

0.536

Gnomad4 FIN exome

AF:

0.475

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.472

GnomAD4 genome

AF:

0.414

AC:

62999

AN:

152118

Hom.:

14100

Cov.:

AF XY:

0.414

AC XY:

30753

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.449

Gnomad4 ASJ

AF:

0.601

Gnomad4 EAS

AF:

0.469

Gnomad4 SAS

AF:

0.518

Gnomad4 FIN

AF:

0.479

Gnomad4 NFE

AF:

0.491

Gnomad4 OTH

AF:

0.445

Alfa

AF:

0.427

Hom.:

1794

Bravo

AF:

0.406

Asia WGS

AF:

0.414

AC:

1441

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

4.5

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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