17-74916083-T-C

Position:

• chr17-74916083-T-C

Variant summary

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

The NM_173477.5(USH1G):​c.*1990A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0358 in 128,730 control chromosomes in the GnomAD database, including 205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (205 hom., cov: 26)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: USH1G NM_173477.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.112

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-74916083-T-C is Benign according to our data. Variant chr17-74916083-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 369224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH1G	NM_173477.5	c.*1990A>G		3_prime_UTR_variant	3/3	ENST00000614341.5
USH1G	NM_001282489.3	c.*1990A>G		3_prime_UTR_variant	3/3
USH1G	XM_011524296.2	c.*1990A>G		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1G	ENST00000614341.5	c.*1990A>G		3_prime_UTR_variant	3/3	1	NM_173477.5	P1

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 4581 AN: 128638 Hom.: 202 Cov.: 26

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.0146

Gnomad EAS AF: 0.000792

Gnomad SAS AF: 0.00213

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0517

Gnomad NFE AF: 0.00207

Gnomad OTH AF: 0.0279

GnomAD4 exome AF: 0.0417 AC: 1 AN: 24 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 1 AN XY: 12

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0358 AC: 4604 AN: 128706 Hom.: 205 Cov.: 26 AF XY: 0.0364 AC XY: 2192 AN XY: 60182

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0286

Gnomad4 ASJ AF: 0.0146

Gnomad4 EAS AF: 0.000793

Gnomad4 SAS AF: 0.00214

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00209

Gnomad4 OTH AF: 0.0305

Alfa AF: 0.0209 Hom.: 16

Bravo AF: 0.0360

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa-deafness syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.9
DANN	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs113905467; hg19: chr17-72912175;