Variant 11-17498317-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000318024.9(USH1C):c.1481-46G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,574,396 control chromosomes in the GnomAD database, including 10,448 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1150 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9298 hom. )

Consequence

USH1C
ENST00000318024.9 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.47

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 11-17498317-C-T is Benign according to our data. Variant chr11-17498317-C-T is described in ClinVar as [Benign]. Clinvar id is 262732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17498317-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_005709.4 linkuse as main transcript	c.1481-46G>A		intron_variant		ENST00000318024.9	NP_005700.2
USH1C	NM_153676.4 linkuse as main transcript	c.2381-46G>A		intron_variant		ENST00000005226.12	NP_710142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12 linkuse as main transcript	c.2381-46G>A		intron_variant		5	NM_153676.4	ENSP00000005226		Q9Y6N9-5
USH1C	ENST00000318024.9 linkuse as main transcript	c.1481-46G>A		intron_variant		1	NM_005709.4	ENSP00000317018	P1	Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16831

AN:

152018

Hom.:

1146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.0824

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.154

Gnomad EAS

AF:

0.305

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0613

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.0988

Gnomad OTH

AF:

0.133

GnomAD3 exomes

AF:

0.122

AC:

30702

AN:

251016

Hom.:

2396

AF XY:

0.120

AC XY:

16274

AN XY:

135642

show subpopulations

Gnomad AFR exome

AF:

0.0890

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.144

Gnomad EAS exome

AF:

0.309

Gnomad SAS exome

AF:

0.110

Gnomad FIN exome

AF:

0.0629

Gnomad NFE exome

AF:

0.0993

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.105

AC:

149521

AN:

1422260

Hom.:

9298

Cov.:

AF XY:

0.106

AC XY:

75088

AN XY:

709866

show subpopulations

Gnomad4 AFR exome

AF:

0.0914

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.144

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0664

Gnomad4 NFE exome

AF:

0.0956

Gnomad4 OTH exome

AF:

0.124

GnomAD4 genome

AF:

0.111

AC:

16855

AN:

152136

Hom.:

1150

Cov.:

AF XY:

0.113

AC XY:

8371

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0917

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.154

Gnomad4 EAS

AF:

0.305

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.0613

Gnomad4 NFE

AF:

0.0987

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.107

Hom.:

265

Bravo

AF:

0.118

Asia WGS

AF:

0.212

AC:

737

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

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

- -

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

-0.88

CADD

Benign

0.010

DANN

Benign

0.77

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