rs10832795

Variant summary

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

The NM_153676.4(USH1C):c.2547-11T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 1,613,404 control chromosomes in the GnomAD database, including 136,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10581 hom., cov: 33)

Exomes 𝑓: 0.41 ( 126029 hom. )

Consequence

USH1C
NM_153676.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0006627

Clinical Significance

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

Conservation

PhyloP100: 1.81

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=-0.66).

BP6

Variant 11-17495688-A-G is Benign according to our data. Variant chr11-17495688-A-G is described in ClinVar as [Benign]. Clinvar id is 48008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17495688-A-G is described in Lovd as [Benign]. Variant chr11-17495688-A-G is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.425 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH1C	NM_005709.4 linkuse as main transcript	c.1646+1070T>C		intron_variant		ENST00000318024.9
USH1C	NM_153676.4 linkuse as main transcript	c.2547-11T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000005226.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1C	ENST00000005226.12 linkuse as main transcript	c.2547-11T>C		splice_polypyrimidine_tract_variant, intron_variant		5	NM_153676.4		Q9Y6N9-5
USH1C	ENST00000318024.9 linkuse as main transcript	c.1646+1070T>C		intron_variant		1	NM_005709.4	P1	Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55137

AN:

152036

Hom.:

10586

Cov.:

show subpopulations

Gnomad AFR

AF:

0.235

Gnomad AMI

AF:

0.350

Gnomad AMR

AF:

0.428

Gnomad ASJ

AF:

0.339

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.419

Gnomad OTH

AF:

0.356

GnomAD3 exomes

AF:

0.410

AC:

103099

AN:

251188

Hom.:

21820

AF XY:

0.412

AC XY:

55943

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.227

Gnomad AMR exome

AF:

0.508

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.298

Gnomad SAS exome

AF:

0.449

Gnomad FIN exome

AF:

0.418

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.430

GnomAD4 exome

AF:

0.412

AC:

602356

AN:

1461250

Hom.:

126029

Cov.:

AF XY:

0.413

AC XY:

300207

AN XY:

726960

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.502

Gnomad4 ASJ exome

AF:

0.354

Gnomad4 EAS exome

AF:

0.306

Gnomad4 SAS exome

AF:

0.447

Gnomad4 FIN exome

AF:

0.419

Gnomad4 NFE exome

AF:

0.417

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.362

AC:

55146

AN:

152154

Hom.:

10581

Cov.:

AF XY:

0.362

AC XY:

26916

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.235

Gnomad4 AMR

AF:

0.429

Gnomad4 ASJ

AF:

0.339

Gnomad4 EAS

AF:

0.306

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.407

Gnomad4 NFE

AF:

0.419

Gnomad4 OTH

AF:

0.351

Alfa

AF:

0.381

Hom.:

3749

Bravo

AF:

0.359

Asia WGS

AF:

0.362

AC:

1259

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Usher syndrome type 1C

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

-0.66

Cadd

Benign

Dann

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00066

dbscSNV1_RF

Benign

0.074

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