rs1013013

Positions:

• chr17-74916770-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173477.5(USH1G):​c.*1303C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,234 control chromosomes in the GnomAD database, including 3,313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3308 hom., cov: 33)
  • Exomes 𝑓: 0.25 (5 hom.)
• Consequence: USH1G NM_173477.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.24

Genes affected

USH1G (HGNC:16356): (USH1 protein network component sans) This gene encodes a protein that contains three ankyrin domains, a class I PDZ-binding motif and a sterile alpha motif. The encoded protein interacts with harmonin, which is associated with Usher syndrome type 1C. This protein plays a role in the development and maintenance of the auditory and visual systems and functions in the cohesion of hair bundles formed by inner ear sensory cells. Mutations in this gene are associated with Usher syndrome type 1G (USH1G). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-74916770-G-A is Benign according to our data. Variant chr17-74916770-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 325034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1G	NM_173477.5	c.*1303C>T		3_prime_UTR_variant	3/3	ENST00000614341.5	NP_775748.2
USH1G	NM_001282489.3	c.*1303C>T		3_prime_UTR_variant	3/3		NP_001269418.1
USH1G	XM_011524296.2	c.*1303C>T		3_prime_UTR_variant	3/3		XP_011522598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1G	ENST00000614341.5	c.*1303C>T		3_prime_UTR_variant	3/3	1	NM_173477.5	ENSP00000480279	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31403 AN: 151986 Hom.: 3311 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.226

GnomAD4 exome AF: 0.254 AC: 33 AN: 130 Hom.: 5 Cov.: 0 AF XY: 0.233 AC XY: 20 AN XY: 86

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.375

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.261

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.206 AC: 31402 AN: 152104 Hom.: 3308 Cov.: 33 AF XY: 0.210 AC XY: 15593 AN XY: 74352

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.223

Alfa AF: 0.205 Hom.: 1328

Bravo AF: 0.199

Asia WGS AF: 0.197 AC: 684 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Usher syndrome type 1G Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.7
DANN	Benign	0.84

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: rs1013013; hg19: chr17-72912862;