rs2237964

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_153676.4(USH1C):c.1414-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 1,487,244 control chromosomes in the GnomAD database, including 16,781 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2492 hom., cov: 32)

Exomes 𝑓: 0.14 ( 14289 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.821

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 11-17510555-C-T is Benign according to our data. Variant chr11-17510555-C-T is described in ClinVar as [Benign]. Clinvar id is 262731.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17510555-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.1414-34G>A		intron_variant	Intron 16 of 26	ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 link	c.1284+6846G>A		intron_variant	Intron 15 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.1414-34G>A		intron_variant	Intron 16 of 26	5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 link	c.1284+6846G>A		intron_variant	Intron 15 of 20	1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25378

AN:

152012

Hom.:

2486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0905

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.0986

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.168

GnomAD3 exomes

AF:

0.162

AC:

40512

AN:

250136

Hom.:

3948

AF XY:

0.161

AC XY:

21845

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.271

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.171

Gnomad EAS exome

AF:

0.0761

Gnomad SAS exome

AF:

0.263

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.121

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.137

AC:

182540

AN:

1335114

Hom.:

14289

Cov.:

AF XY:

0.139

AC XY:

93664

AN XY:

671606

show subpopulations

Gnomad4 AFR exome

AF:

0.274

Gnomad4 AMR exome

AF:

0.230

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.0921

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.102

Gnomad4 NFE exome

AF:

0.119

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.167

AC:

25407

AN:

152130

Hom.:

2492

Cov.:

AF XY:

0.167

AC XY:

12391

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.0905

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.0986

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.169

Alfa

AF:

0.157

Hom.:

413

Bravo

AF:

0.176

Asia WGS

AF:

0.196

AC:

683

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

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 specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Usher syndrome type 1C

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

-0.33

CADD

Benign

DANN

Benign

0.89

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