rs2237958

chr11-17536841-C-Achr11-17536841-C-Gchr11-17536841-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
USH1C	NM_005709.4	c.37-3519G>T		intron_variant		ENST00000318024.9
USH1C	NM_153676.4	c.37-3519G>T		intron_variant		ENST00000005226.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1C	ENST00000005226.12	c.37-3519G>T		intron_variant		5	NM_153676.4
USH1C	ENST00000318024.9	c.37-3519G>T		intron_variant		1	NM_005709.4	P1
USH1C	ENST00000527020.5	c.37-3519G>T		intron_variant		1
USH1C	ENST00000526313.5	c.37-3519G>T		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR AF: 0.582

Gnomad4 AMR AF: 0.528

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.575

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.647

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.546

Alfa AF: 0.432 Hom.: 1434

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

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: rs2237958; hg19: chr11-17558388;