5-90745693-A-G

Position:

chr5-90745693-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_032119.4(ADGRV1):c.10872A>G(p.Gln3624Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.041 in 1,612,324 control chromosomes in the GnomAD database, including 1,614 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 125 hom., cov: 32)

Exomes 𝑓: 0.042 ( 1489 hom. )

Consequence

ADGRV1
NM_032119.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: 0.128

Variant links:

Genes affected

ADGRV1 (HGNC:17416): (adhesion G protein-coupled receptor V1) This gene encodes a member of the G-protein coupled receptor superfamily. The encoded protein contains a 7-transmembrane receptor domain, binds calcium and is expressed in the central nervous system. Mutations in this gene are associated with Usher syndrome 2 and familial febrile seizures. Several alternatively spliced transcripts have been described. [provided by RefSeq, Jul 2008]

ADGRV1 links:

ADGRV1 (HGNC:):

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 5-90745693-A-G is Benign according to our data. Variant chr5-90745693-A-G is described in ClinVar as [Benign]. Clinvar id is 46252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90745693-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.128 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0318 (4840/152296) while in subpopulation AMR AF= 0.0466 (713/15294). AF 95% confidence interval is 0.0438. There are 125 homozygotes in gnomad4. There are 2280 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 125 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.10872A>G	p.Gln3624Gln	synonymous_variant	52/90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.10872A>G	p.Gln3624Gln	synonymous_variant	52/90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4842

AN:

152178

Hom.:

125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00881

Gnomad AMI

AF:

0.0910

Gnomad AMR

AF:

0.0467

Gnomad ASJ

AF:

0.0713

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0447

Gnomad OTH

AF:

0.0502

GnomAD3 exomes

AF:

0.0312

AC:

7750

AN:

248594

Hom.:

197

AF XY:

0.0317

AC XY:

4276

AN XY:

134892

show subpopulations

Gnomad AFR exome

AF:

0.00698

Gnomad AMR exome

AF:

0.0272

Gnomad ASJ exome

AF:

0.0623

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0171

Gnomad FIN exome

AF:

0.0200

Gnomad NFE exome

AF:

0.0434

Gnomad OTH exome

AF:

0.0382

GnomAD4 exome

AF:

0.0420

AC:

61301

AN:

1460028

Hom.:

1489

Cov.:

AF XY:

0.0413

AC XY:

30017

AN XY:

726416

show subpopulations

Gnomad4 AFR exome

AF:

0.00783

Gnomad4 AMR exome

AF:

0.0288

Gnomad4 ASJ exome

AF:

0.0629

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0177

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.0474

Gnomad4 OTH exome

AF:

0.0412

GnomAD4 genome

AF:

0.0318

AC:

4840

AN:

152296

Hom.:

125

Cov.:

AF XY:

0.0306

AC XY:

2280

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00878

Gnomad4 AMR

AF:

0.0466

Gnomad4 ASJ

AF:

0.0713

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.0187

Gnomad4 NFE

AF:

0.0447

Gnomad4 OTH

AF:

0.0497

Alfa

AF:

0.0450

Hom.:

285

Bravo

AF:

0.0344

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.0477

EpiControl

AF:

0.0463

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 20, 2013	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 14, 2011	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 11, 2017	- -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -

Usher syndrome type 2C

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.3

DANN

Benign

0.30

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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