Variant 11-17533367-G-C 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 ENST00000527720.5(USH1C):c.-102C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 1,379,248 control chromosomes in the GnomAD database, including 202,227 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 23430 hom., cov: 28)

Exomes 𝑓: 0.54 ( 178797 hom. )

Consequence

USH1C
ENST00000527720.5 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.38

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=-0.96).

BP6

Variant 11-17533367-G-C is Benign according to our data. Variant chr11-17533367-G-C is described in ClinVar as [Benign]. Clinvar id is 262734.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17533367-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 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.37-45C>G		intron_variant		ENST00000318024.9	NP_005700.2
USH1C	NM_153676.4 linkuse as main transcript	c.37-45C>G		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.37-45C>G		intron_variant		5	NM_153676.4	ENSP00000005226		Q9Y6N9-5
USH1C	ENST00000318024.9 linkuse as main transcript	c.37-45C>G		intron_variant		1	NM_005709.4	ENSP00000317018	P1	Q9Y6N9-1

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

82868

AN:

146130

Hom.:

23409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.632

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.530

Gnomad ASJ

AF:

0.558

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.586

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.532

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.540

AC:

123874

AN:

229536

Hom.:

34151

AF XY:

0.541

AC XY:

67645

AN XY:

124998

show subpopulations

Gnomad AFR exome

AF:

0.603

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.551

Gnomad EAS exome

AF:

0.556

Gnomad SAS exome

AF:

0.585

Gnomad FIN exome

AF:

0.585

Gnomad NFE exome

AF:

0.525

Gnomad OTH exome

AF:

0.560

GnomAD4 exome

AF:

0.535

AC:

659945

AN:

1233008

Hom.:

178797

Cov.:

AF XY:

0.537

AC XY:

335195

AN XY:

624320

show subpopulations

Gnomad4 AFR exome

AF:

0.636

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.557

Gnomad4 EAS exome

AF:

0.573

Gnomad4 SAS exome

AF:

0.589

Gnomad4 FIN exome

AF:

0.601

Gnomad4 NFE exome

AF:

0.523

Gnomad4 OTH exome

AF:

0.551

GnomAD4 genome

AF:

0.567

AC:

82928

AN:

146240

Hom.:

23430

Cov.:

AF XY:

0.569

AC XY:

40382

AN XY:

71026

show subpopulations

Gnomad4 AFR

AF:

0.632

Gnomad4 AMR

AF:

0.530

Gnomad4 ASJ

AF:

0.558

Gnomad4 EAS

AF:

0.566

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.532

Gnomad4 OTH

AF:

0.558

Alfa

AF:

0.324

Hom.:

625

Bravo

AF:

0.581

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 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	-	- -

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

-0.96

CADD

Benign

0.15

DANN

Benign

0.34

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