rs2072227

chr11-17494491-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_153676.4(USH1C):c.2656-115G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 1,219,194 control chromosomes in the GnomAD database, including 126,853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (14718 hom., cov: 33)
  • Exomes 𝑓: 0.45 (112135 hom.)
• Consequence: USH1C NM_153676.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.441

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-17494491-C-T is Benign according to our data. Variant chr11-17494491-C-T is described in ClinVar as [Benign]. Clinvar id is 1233407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH1C	NM_005709.4	c.1647-115G>A		intron_variant		ENST00000318024.9
USH1C	NM_153676.4	c.2656-115G>A		intron_variant		ENST00000005226.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1C	ENST00000005226.12	c.2656-115G>A		intron_variant		5	NM_153676.4
USH1C	ENST00000318024.9	c.1647-115G>A		intron_variant		1	NM_005709.4	P1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66198 AN: 151958 Hom.: 14708 Cov.: 33

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.453 AC: 483428 AN: 1067118 Hom.: 112135 Cov.: 14 AF XY: 0.451 AC XY: 243920 AN XY: 540788

Gnomad4 AFR exome AF: 0.407

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.474

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.436 AC: 66237 AN: 152076 Hom.: 14718 Cov.: 33 AF XY: 0.435 AC XY: 32349 AN XY: 74340

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.432

Alfa AF: 0.457 Hom.: 8550

Bravo AF: 0.425

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.5
Dann	Benign	0.55

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: rs2072227; hg19: chr11-17516038;