rs61749567

Positions:

chr5-90629517-A-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.1817A>C(p.Asn606Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00155 in 1,611,358 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0087 ( 21 hom., cov: 31)

Exomes 𝑓: 0.00081 ( 15 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.86

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=0.009265631).

BP6

Variant 5-90629517-A-C is Benign according to our data. Variant chr5-90629517-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 46296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90629517-A-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00868 (1321/152238) while in subpopulation AFR AF= 0.0307 (1274/41542). AF 95% confidence interval is 0.0293. There are 21 homozygotes in gnomad4. There are 597 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.1817A>C	p.Asn606Thr	missense_variant	9/90	ENST00000405460.9	NP_115495.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.1817A>C	p.Asn606Thr	missense_variant	9/90	1	NM_032119.4	ENSP00000384582	P1	Q8WXG9-1
ADGRV1	ENST00000504142.2 linkuse as main transcript	n.583A>C		non_coding_transcript_exon_variant	3/14	5
ADGRV1	ENST00000640109.1 linkuse as main transcript	n.1913A>C		non_coding_transcript_exon_variant	9/9	5

Frequencies

GnomAD3 genomes

AF:

0.00866

AC:

1317

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00718

GnomAD3 exomes

AF:

0.00218

AC:

537

AN:

246804

Hom.:

AF XY:

0.00163

AC XY:

219

AN XY:

134202

show subpopulations

Gnomad AFR exome

AF:

0.0318

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000626

Gnomad OTH exome

AF:

0.000671

GnomAD4 exome

AF:

0.000810

AC:

1182

AN:

1459120

Hom.:

Cov.:

AF XY:

0.000708

AC XY:

514

AN XY:

725936

show subpopulations

Gnomad4 AFR exome

AF:

0.0293

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000288

Gnomad4 OTH exome

AF:

0.00188

GnomAD4 genome

AF:

0.00868

AC:

1321

AN:

152238

Hom.:

Cov.:

AF XY:

0.00802

AC XY:

597

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0307

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00162

Hom.:

Bravo

AF:

0.00970

ESP6500AA

AF:

0.0328

AC:

121

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.00277

AC:

335

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign/Likely 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 24, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 04, 2015	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 23, 2017	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	Apr 30, 2012	Asn606Thr in Exon 09 of GPR98: This variant is not expected to have clinical sig nificance because it has been identified in 3.2% (96/2992) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs61749567). -

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

.;T

MetaRNN

Benign

0.0093

T;T

MetaSVM

Benign

-0.89

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.0

.;N

REVEL

Benign

0.22

Sift

Benign

0.57

.;T

Sift4G

Pathogenic

0.0

.;D

Polyphen

1.0

D;D

Vest4

0.78

MVP

0.78

MPC

0.23

ClinPred

0.026

GERP RS

5.5

Varity_R

0.24

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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