17-74916891-GCA-G

Position:

• chr17-74916891-GCA-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_173477.5(USH1G):​c.*1180_*1181delTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 152,390 control chromosomes in the GnomAD database, including 349 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (349 hom., cov: 33)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: USH1G NM_173477.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.204

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 -10 ACMG points.

• BP6: Variant 17-74916891-GCA-G is Benign according to our data. Variant chr17-74916891-GCA-G is described in ClinVar as [Likely_benign]. Clinvar id is 325037.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USH1G	NM_173477.5	c.*1180_*1181delTG		3_prime_UTR_variant	3/3	ENST00000614341.5	NP_775748.2
USH1G	NM_001282489.3	c.*1180_*1181delTG		3_prime_UTR_variant	3/3		NP_001269418.1
USH1G	XM_011524296.2	c.*1180_*1181delTG		3_prime_UTR_variant	3/3		XP_011522598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USH1G	ENST00000614341	c.*1180_*1181delTG		3_prime_UTR_variant	3/3	1	NM_173477.5	ENSP00000480279.1

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 5976 AN: 151456 Hom.: 343 Cov.: 33

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.000546

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.0110 AC: 9 AN: 816 Hom.: 0 AF XY: 0.0100 AC XY: 6 AN XY: 598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0286

Gnomad4 FIN exome AF: 0.0294

Gnomad4 NFE exome AF: 0.00828

Gnomad4 OTH exome AF: 0.0172

GnomAD4 genome AF: 0.0396 AC: 6006 AN: 151574 Hom.: 349 Cov.: 33 AF XY: 0.0386 AC XY: 2858 AN XY: 74054

Gnomad4 AFR AF: 0.136

Gnomad4 AMR AF: 0.0163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000546

Gnomad4 OTH AF: 0.0332

Bravo AF: 0.0467

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

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: rs746904393; hg19: chr17-72912983;