Variant 17-74916173-C-G 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.*1900G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,144 control chromosomes in the GnomAD database, including 11,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 11710 hom., cov: 31)

Exomes 𝑓: 0.49 ( 20 hom. )

Consequence

USH1G
NM_173477.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.32

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=-0.8).

BP6

Variant 17-74916173-C-G is Benign according to our data. Variant chr17-74916173-C-G is described in ClinVar as [Benign]. Clinvar id is 325030.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
USH1G	NM_173477.5 linkuse as main transcript	c.*1900G>C	3_prime_UTR_variant	3/3	ENST00000614341.5
USH1G	NM_001282489.3 linkuse as main transcript	c.*1900G>C	3_prime_UTR_variant	3/3
USH1G	XM_011524296.2 linkuse as main transcript	c.*1900G>C	3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH1G	ENST00000614341.5 linkuse as main transcript	c.*1900G>C		3_prime_UTR_variant	3/3	1	NM_173477.5	P1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55725

AN:

151856

Hom.:

11698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.582

Gnomad AMR

AF:

0.513

Gnomad ASJ

AF:

0.273

Gnomad EAS

AF:

0.322

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.481

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.436

Gnomad OTH

AF:

0.363

GnomAD4 exome

AF:

0.488

AC:

AN:

170

Hom.:

Cov.:

AF XY:

0.447

AC XY:

AN XY:

114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.500

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.458

Gnomad4 NFE exome

AF:

0.519

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.367

AC:

55754

AN:

151974

Hom.:

11710

Cov.:

AF XY:

0.374

AC XY:

27755

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.168

Gnomad4 AMR

AF:

0.513

Gnomad4 ASJ

AF:

0.273

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.470

Gnomad4 FIN

AF:

0.481

Gnomad4 NFE

AF:

0.436

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.403

Hom.:

1728

Bravo

AF:

0.357

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

-0.80

Cadd

Benign

6.7

Dann

Benign

0.51

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