rs17703528

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_153676.4(USH1C):c.2226+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 1,612,542 control chromosomes in the GnomAD database, including 4,178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 343 hom., cov: 32)

Exomes 𝑓: 0.060 ( 3835 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.423

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=-0.83).

BP6

Variant 11-17501927-G-A is Benign according to our data. Variant chr11-17501927-G-A is described in ClinVar as [Benign]. Clinvar id is 47995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.2226+12C>T		intron_variant	Intron 21 of 26	ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 link	c.1326+12C>T		intron_variant	Intron 16 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.2226+12C>T		intron_variant	Intron 21 of 26	5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 link	c.1326+12C>T		intron_variant	Intron 16 of 20	1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.0573

AC:

8705

AN:

152030

Hom.:

344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0638

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.0380

Gnomad SAS

AF:

0.199

Gnomad FIN

AF:

0.0355

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0530

Gnomad OTH

AF:

0.0542

GnomAD3 exomes

AF:

0.0645

AC:

16163

AN:

250542

Hom.:

921

AF XY:

0.0711

AC XY:

9620

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.0663

Gnomad AMR exome

AF:

0.0299

Gnomad ASJ exome

AF:

0.0373

Gnomad EAS exome

AF:

0.0275

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.0368

Gnomad NFE exome

AF:

0.0535

Gnomad OTH exome

AF:

0.0587

GnomAD4 exome

AF:

0.0599

AC:

87410

AN:

1460394

Hom.:

3835

Cov.:

AF XY:

0.0636

AC XY:

46170

AN XY:

726474

show subpopulations

Gnomad4 AFR exome

AF:

0.0633

Gnomad4 AMR exome

AF:

0.0313

Gnomad4 ASJ exome

AF:

0.0362

Gnomad4 EAS exome

AF:

0.0362

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.0335

Gnomad4 NFE exome

AF:

0.0526

Gnomad4 OTH exome

AF:

0.0641

GnomAD4 genome

AF:

0.0572

AC:

8701

AN:

152148

Hom.:

343

Cov.:

AF XY:

0.0579

AC XY:

4307

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.0636

Gnomad4 AMR

AF:

0.0422

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.0381

Gnomad4 SAS

AF:

0.199

Gnomad4 FIN

AF:

0.0355

Gnomad4 NFE

AF:

0.0530

Gnomad4 OTH

AF:

0.0551

Alfa

AF:

0.0564

Hom.:

438

Bravo

AF:

0.0549

Asia WGS

AF:

0.120

AC:

419

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Jun 24, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 05, 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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.83

CADD

Benign

DANN

Benign

0.47

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

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