11-17533565-T-C

Position:

• chr11-17533565-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_153676.4(USH1C):​c.37-243A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 613,440 control chromosomes in the GnomAD database, including 97,734 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26383 hom., cov: 32)
  • Exomes 𝑓: 0.55 (71351 hom.)
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.17

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-17533565-T-C is Benign according to our data. Variant chr11-17533565-T-C is described in ClinVar as [Benign]. Clinvar id is 678906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_153676.4	c.37-243A>G		intron_variant		ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.37-243A>G		intron_variant		ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.37-243A>G		intron_variant		5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.37-243A>G		intron_variant		1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88925 AN: 151936 Hom.: 26358 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.553 AC: 255245 AN: 461388 Hom.: 71351 Cov.: 0 AF XY: 0.554 AC XY: 136139 AN XY: 245700

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.553

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.598

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.564

GnomAD4 genome AF: 0.585 AC: 88992 AN: 152052 Hom.: 26383 Cov.: 32 AF XY: 0.588 AC XY: 43687 AN XY: 74328

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.573

Alfa AF: 0.549 Hom.: 11568

Bravo AF: 0.584

Asia WGS AF: 0.612 AC: 2130 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs2883581; hg19: chr11-17555112; COSMIC: COSV50016308; COSMIC: COSV50016308;