Variant chr11-17523544-A-G 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 NM_153676.4(USH1C):c.760-66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 1,533,868 control chromosomes in the GnomAD database, including 262,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24543 hom., cov: 32)

Exomes 𝑓: 0.59 ( 238231 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.902

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=-0.93).

BP6

Variant 11-17523544-A-G is Benign according to our data. Variant chr11-17523544-A-G is described in ClinVar as [Benign]. Clinvar id is 678879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.69 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.760-66T>C		intron_variant		ENST00000318024.9	NP_005700.2
USH1C	NM_153676.4 linkuse as main transcript	c.760-66T>C		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.760-66T>C		intron_variant		5	NM_153676.4	ENSP00000005226		Q9Y6N9-5
USH1C	ENST00000318024.9 linkuse as main transcript	c.760-66T>C		intron_variant		1	NM_005709.4	ENSP00000317018	P1	Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86192

AN:

151922

Hom.:

24496

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.593

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.683

Gnomad SAS

AF:

0.710

Gnomad FIN

AF:

0.520

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.556

GnomAD4 exome

AF:

0.586

AC:

810089

AN:

1381828

Hom.:

238231

AF XY:

0.589

AC XY:

406475

AN XY:

690348

show subpopulations

Gnomad4 AFR exome

AF:

0.533

Gnomad4 AMR exome

AF:

0.629

Gnomad4 ASJ exome

AF:

0.536

Gnomad4 EAS exome

AF:

0.689

Gnomad4 SAS exome

AF:

0.704

Gnomad4 FIN exome

AF:

0.527

Gnomad4 NFE exome

AF:

0.578

Gnomad4 OTH exome

AF:

0.587

GnomAD4 genome

AF:

0.568

AC:

86298

AN:

152040

Hom.:

24543

Cov.:

AF XY:

0.572

AC XY:

42493

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.536

Gnomad4 AMR

AF:

0.593

Gnomad4 ASJ

AF:

0.542

Gnomad4 EAS

AF:

0.683

Gnomad4 SAS

AF:

0.710

Gnomad4 FIN

AF:

0.520

Gnomad4 NFE

AF:

0.571

Gnomad4 OTH

AF:

0.561

Alfa

AF:

0.565

Hom.:

3990

Bravo

AF:

0.568

Asia WGS

AF:

0.705

AC:

2450

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.93

CADD

Benign

0.48

DANN

Benign

0.40

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