11-17501091-G-A

Position:

chr11-17501091-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_153676.4(USH1C):c.2340C>T(p.Val780=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,060 control chromosomes in the GnomAD database, including 61,333 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4221 hom., cov: 33)

Exomes 𝑓: 0.27 ( 57112 hom. )

Consequence

USH1C
NM_153676.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.43

Variant links:

Genes affected

USH1C (HGNC:12597): (USH1 protein network component harmonin) This gene encodes a scaffold protein that functions in the assembly of Usher protein complexes. The protein contains PDZ domains, a coiled-coil region with a bipartite nuclear localization signal and a PEST degradation sequence. Defects in this gene are the cause of Usher syndrome type 1C and non-syndromic sensorineural deafness autosomal recessive type 18. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

USH1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 11-17501091-G-A is Benign according to our data. Variant chr11-17501091-G-A is described in ClinVar as [Benign]. Clinvar id is 47997.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17501091-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.43 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH1C	NM_153676.4 linkuse as main transcript	c.2340C>T	p.Val780=	synonymous_variant	23/27	ENST00000005226.12
USH1C	NM_005709.4 linkuse as main transcript	c.1440C>T	p.Val480=	synonymous_variant	18/21	ENST00000318024.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1C	ENST00000005226.12 linkuse as main transcript	c.2340C>T	p.Val780=	synonymous_variant	23/27	5	NM_153676.4		Q9Y6N9-5
USH1C	ENST00000318024.9 linkuse as main transcript	c.1440C>T	p.Val480=	synonymous_variant	18/21	1	NM_005709.4	P1	Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.214

AC:

32544

AN:

152044

Hom.:

4221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0534

Gnomad AMI

AF:

0.249

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.351

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.285

Gnomad OTH

AF:

0.242

GnomAD3 exomes

AF:

0.254

AC:

63640

AN:

250336

Hom.:

8785

AF XY:

0.258

AC XY:

34945

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.0470

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.352

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.289

Gnomad OTH exome

AF:

0.276

GnomAD4 exome

AF:

0.275

AC:

401161

AN:

1460898

Hom.:

57112

Cov.:

AF XY:

0.273

AC XY:

198318

AN XY:

726748

show subpopulations

Gnomad4 AFR exome

AF:

0.0449

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.358

Gnomad4 EAS exome

AF:

0.310

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.285

Gnomad4 NFE exome

AF:

0.286

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.214

AC:

32538

AN:

152162

Hom.:

4221

Cov.:

AF XY:

0.214

AC XY:

15923

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0533

Gnomad4 AMR

AF:

0.225

Gnomad4 ASJ

AF:

0.351

Gnomad4 EAS

AF:

0.281

Gnomad4 SAS

AF:

0.195

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.285

Gnomad4 OTH

AF:

0.238

Alfa

AF:

0.268

Hom.:

3894

Bravo

AF:

0.205

Asia WGS

AF:

0.206

AC:

715

AN:

3478

EpiCase

AF:

0.298

EpiControl

AF:

0.304

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Usher syndrome type 1C

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 24, 2009	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Autosomal recessive nonsyndromic hearing loss 18A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

2.4

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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