chr11-17527112-A-C

Position:

• chr11-17527112-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_153676.4(USH1C):​c.497-72T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (156 hom., cov: 9)
  • Exomes 𝑓: 0.022 (374 hom.)
  • Failed GnomAD Quality Control
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1C	NM_153676.4	c.497-72T>G		intron_variant		ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.497-72T>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.497-72T>G		intron_variant		5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.497-72T>G		intron_variant		1	NM_005709.4	ENSP00000317018.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2461 AN: 66538 Hom.: 154 Cov.: 9 FAILED QC

Gnomad AFR AF: 0.0655

Gnomad AMI AF: 0.0221

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0180

Gnomad EAS AF: 0.0920

Gnomad SAS AF: 0.0436

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00735

Gnomad NFE AF: 0.0191

Gnomad OTH AF: 0.0433

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0217 AC: 17158 AN: 791816 Hom.: 374 Cov.: 25 AF XY: 0.0220 AC XY: 8648 AN XY: 392992

Gnomad4 AFR exome AF: 0.0930

Gnomad4 AMR exome AF: 0.0359

Gnomad4 ASJ exome AF: 0.00869

Gnomad4 EAS exome AF: 0.0991

Gnomad4 SAS exome AF: 0.0260

Gnomad4 FIN exome AF: 0.00595

Gnomad4 NFE exome AF: 0.0157

Gnomad4 OTH exome AF: 0.0253

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0371 AC: 2470 AN: 66584 Hom.: 156 Cov.: 9 AF XY: 0.0390 AC XY: 1199 AN XY: 30752

Gnomad4 AFR AF: 0.0656

Gnomad4 AMR AF: 0.0453

Gnomad4 ASJ AF: 0.0180

Gnomad4 EAS AF: 0.0920

Gnomad4 SAS AF: 0.0436

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0191

Gnomad4 OTH AF: 0.0448

Alfa AF: 0.282 Hom.: 68

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.75
DANN	Benign	0.076

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: rs28671305; hg19: chr11-17548659; COSMIC: COSV50024155;