rs2237958

Variant names:

• chr11-17536841-C-A
• rs2237958
• NM_153676.4:c.37-3519G>T

Your query was ambiguous. Multiple possible variants found:

• chr11-17536841-C-A
• chr11-17536841-C-G
• chr11-17536841-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153676.4(USH1C):​c.37-3519G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 152,146 control chromosomes in the GnomAD database, including 23,738 homozygotes. 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 0.56 (23738 hom., cov: 33)
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• Usher syndrome type 1

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 1C

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
• autosomal recessive nonsyndromic hearing loss 18A

  Inheritance: AR, Unknown Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
USH1C	NM_153676.4	c.37-3519G>T		intron_variant	Intron 1 of 26	ENST00000005226.12	NP_710142.1
USH1C	NM_005709.4	c.37-3519G>T		intron_variant	Intron 1 of 20	ENST00000318024.9	NP_005700.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH1C	ENST00000005226.12	c.37-3519G>T		intron_variant	Intron 1 of 26	5	NM_153676.4	ENSP00000005226.7
USH1C	ENST00000318024.9	c.37-3519G>T		intron_variant	Intron 1 of 20	1	NM_005709.4	ENSP00000317018.4
USH1C	ENST00000527020.5	c.37-3519G>T		intron_variant	Intron 1 of 19	1		ENSP00000436934.1
USH1C	ENST00000526313.5	n.37-3519G>T		intron_variant	Intron 1 of 19	1		ENSP00000432236.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84803 AN: 152028 Hom.: 23725 Cov.: 33

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.574

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.546

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.558 AC: 84852 AN: 152146 Hom.: 23738 Cov.: 33 AF XY: 0.560 AC XY: 41681 AN XY: 74378

African (AFR) AF: 0.582 AC: 24165 AN: 41522

American (AMR) AF: 0.528 AC: 8075 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1989 AN: 3472

East Asian (EAS) AF: 0.575 AC: 2972 AN: 5170

South Asian (SAS) AF: 0.595 AC: 2862 AN: 4812

European-Finnish (FIN) AF: 0.647 AC: 6858 AN: 10592

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36272 AN: 67972

Other (OTH) AF: 0.546 AC: 1152 AN: 2110

Alfa AF: 0.442 Hom.: 1567

Bravo AF: 0.553

Asia WGS AF: 0.604 AC: 2103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.44
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2237958; hg19: chr11-17558388;