rs2190454

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.1261-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.698 in 1,611,520 control chromosomes in the GnomAD database, including 393,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.70 ( 37318 hom., cov: 32)

Exomes 𝑓: 0.70 ( 356530 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0700

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=-0.84).

BP6

Variant 11-17512088-G-A is Benign according to our data. Variant chr11-17512088-G-A is described in ClinVar as [Benign]. Clinvar id is 670417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17512088-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4 link	c.1261-34C>T		intron_variant	Intron 15 of 26	ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 link	c.1284+5313C>T		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.1261-34C>T		intron_variant	Intron 15 of 26	5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 link	c.1284+5313C>T		intron_variant	Intron 15 of 20	1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.700

AC:

106436

AN:

151962

Hom.:

37285

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.736

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.714

Gnomad SAS

AF:

0.797

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.689

Gnomad OTH

AF:

0.681

GnomAD3 exomes

AF:

0.717

AC:

179728

AN:

250676

Hom.:

64961

AF XY:

0.715

AC XY:

96949

AN XY:

135640

show subpopulations

Gnomad AFR exome

AF:

0.698

Gnomad AMR exome

AF:

0.812

Gnomad ASJ exome

AF:

0.605

Gnomad EAS exome

AF:

0.703

Gnomad SAS exome

AF:

0.790

Gnomad FIN exome

AF:

0.717

Gnomad NFE exome

AF:

0.684

Gnomad OTH exome

AF:

0.697

GnomAD4 exome

AF:

0.698

AC:

1018019

AN:

1459440

Hom.:

356530

Cov.:

AF XY:

0.700

AC XY:

508188

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.692

Gnomad4 AMR exome

AF:

0.805

Gnomad4 ASJ exome

AF:

0.600

Gnomad4 EAS exome

AF:

0.721

Gnomad4 SAS exome

AF:

0.788

Gnomad4 FIN exome

AF:

0.715

Gnomad4 NFE exome

AF:

0.688

Gnomad4 OTH exome

AF:

0.691

GnomAD4 genome

AF:

0.700

AC:

106521

AN:

152080

Hom.:

37318

Cov.:

AF XY:

0.704

AC XY:

52378

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.692

Gnomad4 AMR

AF:

0.752

Gnomad4 ASJ

AF:

0.602

Gnomad4 EAS

AF:

0.714

Gnomad4 SAS

AF:

0.796

Gnomad4 FIN

AF:

0.716

Gnomad4 NFE

AF:

0.689

Gnomad4 OTH

AF:

0.686

Alfa

AF:

0.683

Hom.:

20423

Bravo

AF:

0.699

Asia WGS

AF:

0.769

AC:

2676

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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. -

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

-0.84

CADD

Benign

3.7

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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