9-114482852-G-A

Position:

• chr9-114482852-G-A

Variant summary

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

The NM_015404.4(WHRN):​c.619-4081C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,126 control chromosomes in the GnomAD database, including 1,638 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 0.13 (1638 hom., cov: 31)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WHRN	NM_015404.4	c.619-4081C>T		intron_variant		ENST00000362057.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WHRN	ENST00000362057.4	c.619-4081C>T		intron_variant		1	NM_015404.4	P1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19851 AN: 152006 Hom.: 1636 Cov.: 31

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.130 AC: 19845 AN: 152126 Hom.: 1638 Cov.: 31 AF XY: 0.128 AC XY: 9542 AN XY: 74358

Gnomad4 AFR AF: 0.0355

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.138

Alfa AF: 0.174 Hom.: 2370

Bravo AF: 0.127

Asia WGS AF: 0.139 AC: 483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.66

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: rs16929545; hg19: chr9-117245132;