Variant chr11-17526468-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 NM_153676.4(USH1C):c.580-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,603,294 control chromosomes in the GnomAD database, including 72,172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7036 hom., cov: 33)

Exomes 𝑓: 0.30 ( 65136 hom. )

Consequence

USH1C
NM_153676.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.974

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:

USH1C (HGNC:):

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=-0.79).

BP6

Variant 11-17526468-C-T is Benign according to our data. Variant chr11-17526468-C-T is described in ClinVar as [Benign]. Clinvar id is 262738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17526468-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_153676.4 linkuse as main transcript	c.580-27G>A		intron_variant		ENST00000005226.12	NP_710142.1	Q9Y6N9-5
USH1C	NM_005709.4 linkuse as main transcript	c.580-27G>A		intron_variant		ENST00000318024.9	NP_005700.2	Q9Y6N9-1A0A0S2Z4U9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12 linkuse as main transcript	c.580-27G>A		intron_variant		5	NM_153676.4	ENSP00000005226.7		Q9Y6N9-5
USH1C	ENST00000318024.9 linkuse as main transcript	c.580-27G>A		intron_variant		1	NM_005709.4	ENSP00000317018.4		Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.302

AC:

45959

AN:

151994

Hom.:

7028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.251

Gnomad AMR

AF:

0.324

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.267

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.308

GnomAD3 exomes

AF:

0.313

AC:

76142

AN:

243178

Hom.:

12171

AF XY:

0.309

AC XY:

40629

AN XY:

131574

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.296

Gnomad EAS exome

AF:

0.504

Gnomad SAS exome

AF:

0.266

Gnomad FIN exome

AF:

0.287

Gnomad NFE exome

AF:

0.293

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.297

AC:

430672

AN:

1451180

Hom.:

65136

Cov.:

AF XY:

0.295

AC XY:

213237

AN XY:

722352

show subpopulations

Gnomad4 AFR exome

AF:

0.295

Gnomad4 AMR exome

AF:

0.349

Gnomad4 ASJ exome

AF:

0.301

Gnomad4 EAS exome

AF:

0.515

Gnomad4 SAS exome

AF:

0.268

Gnomad4 FIN exome

AF:

0.289

Gnomad4 NFE exome

AF:

0.289

Gnomad4 OTH exome

AF:

0.303

GnomAD4 genome

AF:

0.302

AC:

45977

AN:

152114

Hom.:

7036

Cov.:

AF XY:

0.301

AC XY:

22384

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.293

Gnomad4 AMR

AF:

0.324

Gnomad4 ASJ

AF:

0.304

Gnomad4 EAS

AF:

0.501

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.286

Gnomad4 NFE

AF:

0.294

Gnomad4 OTH

AF:

0.306

Alfa

AF:

0.274

Hom.:

2738

Bravo

AF:

0.308

Asia WGS

AF:

0.352

AC:

1222

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 24, 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

-0.79

CADD

Benign

8.9

DANN

Benign

0.57

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