rs5789990

Positions:

• chr11-17526854-CG-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_153676.4(USH1C):​c.522-45del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7619 hom., cov: 0)
  • Exomes 𝑓: 0.32 (75262 hom.)
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.190

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 11-17526854-CG-C is Benign according to our data. Variant chr11-17526854-CG-C is described in ClinVar as [Benign]. Clinvar id is 262737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17526854-CG-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH1C	NM_005709.4	c.522-45del		intron_variant		ENST00000318024.9
USH1C	NM_153676.4	c.522-45del		intron_variant		ENST00000005226.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1C	ENST00000005226.12	c.522-45del		intron_variant		5	NM_153676.4
USH1C	ENST00000318024.9	c.522-45del		intron_variant		1	NM_005709.4	P1

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47754 AN: 151816 Hom.: 7610 Cov.: 0

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.332

GnomAD3 exomes AF: 0.330 AC: 81327 AN: 246610 Hom.: 13638 AF XY: 0.327 AC XY: 43482 AN XY: 133088

Gnomad AFR exome AF: 0.283

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.506

Gnomad SAS exome AF: 0.277

Gnomad FIN exome AF: 0.295

Gnomad NFE exome AF: 0.318

Gnomad OTH exome AF: 0.336

GnomAD4 exome AF: 0.319 AC: 464102 AN: 1454582 Hom.: 75262 Cov.: 0 AF XY: 0.317 AC XY: 229760 AN XY: 723766

Gnomad4 AFR exome AF: 0.282

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.516

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.323

GnomAD4 genome AF: 0.314 AC: 47776 AN: 151934 Hom.: 7619 Cov.: 0 AF XY: 0.312 AC XY: 23202 AN XY: 74256

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.292

Gnomad4 NFE AF: 0.318

Gnomad4 OTH AF: 0.330

Alfa AF: 0.209 Hom.: 649

Bravo AF: 0.321

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 24, 2018

- -

Usher syndrome type 1C Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs5789990; hg19: chr11-17548401;