rs145294917

Positions:

chr5-90745617-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032119.4(ADGRV1):c.10796G>C(p.Gly3599Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000643 in 1,611,954 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 7 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.22

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009105235).

BP6

Variant 5-90745617-G-C is Benign according to our data. Variant chr5-90745617-G-C is described in ClinVar as [Benign]. Clinvar id is 163596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90745617-G-C is described in Lovd as [Benign]. Variant chr5-90745617-G-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00362 (551/152210) while in subpopulation AFR AF= 0.0121 (504/41538). AF 95% confidence interval is 0.0113. There are 1 homozygotes in gnomad4. There are 252 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.10796G>C	p.Gly3599Ala	missense_variant	52/90	ENST00000405460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.10796G>C	p.Gly3599Ala	missense_variant	52/90	1	NM_032119.4	P1	Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.00362

AC:

551

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.000898

AC:

223

AN:

248350

Hom.:

AF XY:

0.000601

AC XY:

AN XY:

134720

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000499

GnomAD4 exome

AF:

0.000333

AC:

486

AN:

1459744

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

726206

show subpopulations

Gnomad4 AFR exome

AF:

0.0120

Gnomad4 AMR exome

AF:

0.000470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.000863

GnomAD4 genome

AF:

0.00362

AC:

551

AN:

152210

Hom.:

Cov.:

AF XY:

0.00339

AC XY:

252

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0121

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.000572

Hom.:

Bravo

AF:

0.00407

ESP6500AA

AF:

0.0131

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00109

AC:

132

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 04, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	Gly3599Ala in Exon 52 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 1.4% (40/2958) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs145294917). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

ADGRV1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

.;T

MetaRNN

Benign

0.0091

T;T

MetaSVM

Benign

-0.34

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.4

.;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.018

.;D

Sift4G

Pathogenic

0.0

.;D

Polyphen

1.0

D;D

Vest4

0.64

MVP

0.66

MPC

0.34

ClinPred

0.058

GERP RS

4.1

Varity_R

0.42

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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