5-90712327-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_032119.4(ADGRV1):c.9083A>G(p.Asn3028Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000156 in 1,557,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. N3028N) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000088 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 4.94

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

Usher syndrome type 2
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
febrile seizures, familial, 4
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
nonsyndromic genetic hearing loss
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ADGRV1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008969128).

BP6

Variant 5-90712327-A-G is Benign according to our data. Variant chr5-90712327-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 197473.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032119.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.9083A>G	p.Asn3028Ser	missense	Exon 42 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.9099A>G		non_coding_transcript_exon	Exon 42 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.9083A>G	p.Asn3028Ser	missense	Exon 42 of 90	ENSP00000384582.2
ADGRV1	ENST00000509621.1	TSL:1	n.1780A>G		non_coding_transcript_exon	Exon 10 of 26
ADGRV1	ENST00000639473.1	TSL:5	n.4542A>G		non_coding_transcript_exon	Exon 22 of 23

Frequencies

GnomAD3 genomes

AF:

0.000788

AC:

120

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000217

AC:

AN:

179420

AF XY:

0.000168

show subpopulations

Gnomad AFR exome

AF:

0.00303

Gnomad AMR exome

AF:

0.0000372

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000296

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000205

GnomAD4 exome

AF:

0.0000876

AC:

123

AN:

1404692

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

694276

show subpopulations

African (AFR)

AF:

0.00233

AC:

AN:

32190

American (AMR)

AF:

0.0000265

AC:

AN:

37784

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25340

East Asian (EAS)

AF:

0.000265

AC:

AN:

37704

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79680

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50188

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5282

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078322

Other (OTH)

AF:

0.000584

AC:

AN:

58202

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000788

AC:

120

AN:

152338

Hom.:

Cov.:

AF XY:

0.000752

AC XY:

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.00279

AC:

116

AN:

41586

American (AMR)

AF:

0.000131

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000536

Hom.:

Bravo

AF:

0.000903

ESP6500AA

AF:

0.00362

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000272

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 11, 2014

Eurofins Ntd Llc (ga)

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Apr 17, 2019

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Aug 24, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Asn3028Ser in exon 42 of GPR98: This variant is not expected to have clinical significance because it has been identified in 0.6% (18/2968) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs150549897).

ADGRV1-related disorder

Benign:1

Jan 03, 2024

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.057

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.55

M_CAP

Benign

0.013

MetaRNN

Benign

0.0090

MetaSVM

Benign

-1.1

PhyloP100

4.9

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.37

REVEL

Benign

0.090

Sift

Benign

0.41

Sift4G

Uncertain

0.034

Polyphen

0.028

Vest4

0.17

MVP

0.40

MPC

0.041

ClinPred

0.027

GERP RS

5.8

Varity_R

0.035

gMVP

0.080

Mutation Taster

=84/16

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over