rs10982200

chr9-114406271-C-Achr9-114406271-C-Gchr9-114406271-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015404.4(WHRN):c.2236+84G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,586,008 control chromosomes in the GnomAD database, including 187,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (14059 hom., cov: 33)
  • Exomes 𝑓: 0.49 (173789 hom.)
• Consequence: WHRN NM_015404.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.57

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-114406271-C-A is Benign according to our data. Variant chr9-114406271-C-A is described in ClinVar as [Benign]. Clinvar id is 1180085.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr9-114406271-C-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WHRN	NM_015404.4	c.2236+84G>T		intron_variant		ENST00000362057.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WHRN	ENST00000362057.4	c.2236+84G>T		intron_variant		1	NM_015404.4	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62915 AN: 152020 Hom.: 14052 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.599

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.489 AC: 701665 AN: 1433868 Hom.: 173789 AF XY: 0.492 AC XY: 351616 AN XY: 714488

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.503

Gnomad4 SAS exome AF: 0.538

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.492

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.414 AC: 62939 AN: 152140 Hom.: 14059 Cov.: 33 AF XY: 0.413 AC XY: 30718 AN XY: 74372

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.599

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.441

Alfa AF: 0.281 Hom.: 688

Bravo AF: 0.405

Asia WGS AF: 0.412 AC: 1434 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.10
Dann	Benign	0.54

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: rs10982200; hg19: chr9-117168551; COSMIC: COSV54326796;