9-114488113-A-G

Position:

• chr9-114488113-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000362057.4(WHRN):​c.619-9342T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,074 control chromosomes in the GnomAD database, including 14,283 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.40 (14283 hom., cov: 32)
• Consequence: WHRN ENST00000362057.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WHRN	NM_015404.4	c.619-9342T>C		intron_variant		ENST00000362057.4	NP_056219.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WHRN	ENST00000362057.4	c.619-9342T>C		intron_variant		1	NM_015404.4	ENSP00000354623	P1

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60090 AN: 151956 Hom.: 14284 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.447

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.395 AC: 60090 AN: 152074 Hom.: 14283 Cov.: 32 AF XY: 0.393 AC XY: 29241 AN XY: 74312

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.475

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.449

Alfa AF: 0.479 Hom.: 10722

Bravo AF: 0.384

Asia WGS AF: 0.522 AC: 1814 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs10982246; hg19: chr9-117250393; COSMIC: COSV54329121; COSMIC: COSV54329121;