chr9-114467120-T-G

Position:

• chr9-114467120-T-G

Variant summary

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

The NM_015404.4(WHRN):​c.838-728A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 149,982 control chromosomes in the GnomAD database, including 34,514 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 0.66 (34514 hom., cov: 28)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.907 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WHRN	NM_015404.4	c.838-728A>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.838-728A>C		intron_variant		1	NM_015404.4	ENSP00000354623	P1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 99608 AN: 149858 Hom.: 34487 Cov.: 28

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.679

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.862

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.682

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

GnomAD4 genome AF: 0.665 AC: 99677 AN: 149982 Hom.: 34514 Cov.: 28 AF XY: 0.666 AC XY: 48819 AN XY: 73278

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.679

Gnomad4 EAS AF: 0.929

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.683

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.685

Alfa AF: 0.722 Hom.: 50218

Bravo AF: 0.659

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.37

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: rs1535971; hg19: chr9-117229400; COSMIC: COSV54328982;