chr5-90745103-G-A

Position:

chr5-90745103-G-A

Variant summary

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

The NM_032119.4(ADGRV1):c.10607G>A(p.Arg3536His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000955 in 1,613,714 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 5 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.193

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=0.006443411).

BP6

Variant 5-90745103-G-A is Benign according to our data. Variant chr5-90745103-G-A is described in ClinVar as [Benign]. Clinvar id is 46250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90745103-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00309 (470/152186) while in subpopulation AFR AF= 0.0099 (411/41532). AF 95% confidence interval is 0.00911. There are 3 homozygotes in gnomad4. There are 221 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.10607G>A	p.Arg3536His	missense_variant	51/90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 link	c.10607G>A	p.Arg3536His	missense_variant	51/90	1	NM_032119.4	ENSP00000384582.2		Q8WXG9-1

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

465

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00980

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

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:

0.000265

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00100

AC:

250

AN:

249104

Hom.:

AF XY:

0.000858

AC XY:

116

AN XY:

135122

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.000666

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000360

Gnomad FIN exome

AF:

0.0000928

Gnomad NFE exome

AF:

0.000372

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000733

AC:

1071

AN:

1461528

Hom.:

Cov.:

AF XY:

0.000675

AC XY:

491

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.000961

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000485

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00309

AC:

470

AN:

152186

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00990

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000958

Hom.:

Bravo

AF:

0.00378

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0104

AC:

ESP6500EA

AF:

0.00110

AC:

ExAC

AF:

0.00125

AC:

151

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 27, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 26, 2012

Arg3536His in exon 51 of GPR98: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, has been identified in 0.12% (8/660) of Europea n American chromosomes and 1.1% (33/3068) of African American chromosomes in a b road population by the NHLBI Exome sequencing project (http://evs.gs.washington. edu/EVS/; rs144618536). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.1

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.14

.;T

MetaRNN

Benign

0.0064

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.49

.;N

REVEL

Benign

0.067

Sift

Benign

0.54

.;T

Sift4G

Benign

0.16

.;T

Polyphen

0.045

B;B

Vest4

0.11

MVP

0.28

MPC

0.056

ClinPred

0.0045

GERP RS

4.3

Varity_R

0.022

gMVP

0.29

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