NM_032119.4:c.8876G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032119.4(ADGRV1):c.8876G>A(p.Arg2959Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00465 in 1,610,828 control chromosomes in the GnomAD database, including 305 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.025 ( 158 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 147 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.03

Publications

5 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: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023107529).

BP6

Variant 5-90711032-G-A is Benign according to our data. Variant chr5-90711032-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 46400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.8876G>A	p.Arg2959Gln	missense	Exon 40 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.8892G>A		non_coding_transcript_exon	Exon 40 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.8876G>A	p.Arg2959Gln	missense	Exon 40 of 90	ENSP00000384582.2
ADGRV1	ENST00000509621.1	TSL:1	n.1573G>A		non_coding_transcript_exon	Exon 8 of 26
ADGRV1	ENST00000639473.1	TSL:5	n.4335G>A		non_coding_transcript_exon	Exon 20 of 23

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3873

AN:

152124

Hom.:

158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0891

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00891

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00634

AC:

1567

AN:

247306

AF XY:

0.00455

show subpopulations

Gnomad AFR exome

AF:

0.0904

Gnomad AMR exome

AF:

0.00423

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000116

Gnomad OTH exome

AF:

0.00299

GnomAD4 exome

AF:

0.00248

AC:

3615

AN:

1458588

Hom.:

147

Cov.:

AF XY:

0.00212

AC XY:

1535

AN XY:

725404

show subpopulations

African (AFR)

AF:

0.0903

AC:

3014

AN:

33388

American (AMR)

AF:

0.00422

AC:

188

AN:

44598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.000164

AC:

AN:

85426

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53240

Middle Eastern (MID)

AF:

0.00312

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

1110218

Other (OTH)

AF:

0.00543

AC:

327

AN:

60258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

147

294

442

589

736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.0255

AC:

3875

AN:

152240

Hom.:

158

Cov.:

AF XY:

0.0246

AC XY:

1832

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0889

AC:

3692

AN:

41540

American (AMR)

AF:

0.00890

AC:

136

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000176

AC:

AN:

68014

Other (OTH)

AF:

0.0156

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

185

370

555

740

925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.00844

Hom.:

127

Bravo

AF:

0.0295

ESP6500AA

AF:

0.0847

AC:

309

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.00805

AC:

973

Asia WGS

AF:

0.00462

AC:

AN:

3474

EpiCase

AF:

0.000221

EpiControl

AF:

0.000120

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C (1)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.10

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

PhyloP100

1.0

PrimateAI

Benign

0.19

PROVEAN

Benign

-1.5

REVEL

Benign

0.032

Sift

Benign

0.56

Sift4G

Benign

0.24

Polyphen

0.20

Vest4

0.086

MVP

0.28

MPC

0.33

ClinPred

0.021

GERP RS

3.0

Varity_R

0.060

gMVP

0.36

Mutation Taster

=86/14

polymorphism (auto)

(source)

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

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

Computational scores

Splicing

Publications

Other links and lift over