Variant 17-74916961-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_173477.5(USH1G):c.*1112C>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 0.0179 in 150,610 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 79 hom., cov: 34)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

USH1G
NM_173477.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.18

Variant links:

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]

USH1G links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 17-74916961-G-A is Benign according to our data. Variant chr17-74916961-G-A is described in ClinVar as [Benign]. Clinvar id is 890034.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
USH1G	NM_173477.5 link	c.*1112C>T	3_prime_UTR_variant	3/3	ENST00000614341.5	NP_775748.2
USH1G	NM_001282489.3 link	c.*1112C>T	3_prime_UTR_variant	3/3		NP_001269418.1	Q495M9B4DL95
USH1G	XM_011524296.2 link	c.*1112C>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 link	c.*1112C>T		3_prime_UTR_variant	3/3	1	NM_173477.5	ENSP00000480279.1		Q495M9

Frequencies

GnomAD3 genomes

AF:

0.0180

AC:

2690

AN:

149566

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0630

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00640

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000596

Gnomad SAS

AF:

0.000431

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000356

Gnomad OTH

AF:

0.00787

GnomAD4 exome

AF:

0.00108

AC:

AN:

924

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

AN XY:

656

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0180

AC:

2693

AN:

149686

Hom.:

Cov.:

AF XY:

0.0172

AC XY:

1255

AN XY:

72976

show subpopulations

Gnomad4 AFR

AF:

0.0629

Gnomad4 AMR

AF:

0.00639

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000598

Gnomad4 SAS

AF:

0.000431

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000356

Gnomad4 OTH

AF:

0.00779

Alfa

AF:

0.000284

Hom.:

Bravo

AF:

0.0202

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Usher syndrome type 1G

Benign:1

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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.98

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over