11-17521006-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153676.4(USH1C):c.1086-12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0502 in 1,613,244 control chromosomes in the GnomAD database, including 3,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 909 hom., cov: 31)

Exomes 𝑓: 0.046 ( 2180 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Splicing: ADA: 0.00004067

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.118

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 11-17521006-C-T is Benign according to our data. Variant chr11-17521006-C-T is described in ClinVar as [Benign]. Clinvar id is 47974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17521006-C-T is described in Lovd as [Benign]. Variant chr11-17521006-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.1086-12G>A		intron_variant	Intron 13 of 26	ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 link	c.1086-12G>A		intron_variant	Intron 13 of 20	ENST00000318024.9	NP_005700.2	Q9Y6N9-1A0A0S2Z4U9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12 link	c.1086-12G>A		intron_variant	Intron 13 of 26	5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 link	c.1086-12G>A		intron_variant	Intron 13 of 20	1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.0861

AC:

13084

AN:

152014

Hom.:

897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0881

Gnomad ASJ

AF:

0.0859

Gnomad EAS

AF:

0.0316

Gnomad SAS

AF:

0.0208

Gnomad FIN

AF:

0.0364

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0402

Gnomad OTH

AF:

0.0852

GnomAD3 exomes

AF:

0.0603

AC:

15159

AN:

251444

Hom.:

722

AF XY:

0.0550

AC XY:

7469

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.191

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.0919

Gnomad EAS exome

AF:

0.0313

Gnomad SAS exome

AF:

0.0280

Gnomad FIN exome

AF:

0.0369

Gnomad NFE exome

AF:

0.0434

Gnomad OTH exome

AF:

0.0634

GnomAD4 exome

AF:

0.0465

AC:

67897

AN:

1461112

Hom.:

2180

Cov.:

AF XY:

0.0454

AC XY:

33004

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.196

Gnomad4 AMR exome

AF:

0.101

Gnomad4 ASJ exome

AF:

0.0869

Gnomad4 EAS exome

AF:

0.0364

Gnomad4 SAS exome

AF:

0.0277

Gnomad4 FIN exome

AF:

0.0404

Gnomad4 NFE exome

AF:

0.0402

Gnomad4 OTH exome

AF:

0.0567

GnomAD4 genome

AF:

0.0864

AC:

13138

AN:

152132

Hom.:

909

Cov.:

AF XY:

0.0843

AC XY:

6271

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.191

Gnomad4 AMR

AF:

0.0881

Gnomad4 ASJ

AF:

0.0859

Gnomad4 EAS

AF:

0.0316

Gnomad4 SAS

AF:

0.0206

Gnomad4 FIN

AF:

0.0364

Gnomad4 NFE

AF:

0.0402

Gnomad4 OTH

AF:

0.0844

Alfa

AF:

0.0617

Hom.:

167

Bravo

AF:

0.0964

Asia WGS

AF:

0.0420

AC:

144

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 24, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 30, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Usher syndrome type 1C

Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Autosomal recessive nonsyndromic hearing loss 18A

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000041

dbscSNV1_RF

Benign

0.060

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