NM_032119.4:c.9743G>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.9743G>A(p.Gly3248Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.138 in 1,608,614 control chromosomes in the GnomAD database, including 17,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 1968 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15453 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 7.96

Publications

34 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:

LOC105379077 (HGNC:):

LOC105379077 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=0.0027834475).

BP6

Variant 5-90721054-G-A is Benign according to our data. Variant chr5-90721054-G-A is described in ClinVar as Benign. ClinVar VariationId is 46407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.392 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.9743G>A	p.Gly3248Asp	missense	Exon 45 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.9759G>A		non_coding_transcript_exon	Exon 45 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.9743G>A	p.Gly3248Asp	missense	Exon 45 of 90	ENSP00000384582.2
ADGRV1	ENST00000509621.1	TSL:1	n.2440G>A		non_coding_transcript_exon	Exon 13 of 26
ADGRV1	ENST00000640374.1	TSL:5	n.2887G>A		non_coding_transcript_exon	Exon 15 of 27

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22996

AN:

151816

Hom.:

1955

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.0976

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.202

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.156

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.167

GnomAD2 exomes

AF:

0.166

AC:

41104

AN:

247700

AF XY:

0.166

show subpopulations

Gnomad AFR exome

AF:

0.158

Gnomad AMR exome

AF:

0.133

Gnomad ASJ exome

AF:

0.205

Gnomad EAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.155

GnomAD4 exome

AF:

0.136

AC:

198326

AN:

1456680

Hom.:

15453

Cov.:

AF XY:

0.138

AC XY:

100235

AN XY:

724662

show subpopulations

African (AFR)

AF:

0.160

AC:

5346

AN:

33340

American (AMR)

AF:

0.134

AC:

5971

AN:

44510

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

5161

AN:

25992

East Asian (EAS)

AF:

0.371

AC:

14639

AN:

39450

South Asian (SAS)

AF:

0.196

AC:

16758

AN:

85692

European-Finnish (FIN)

AF:

0.163

AC:

8655

AN:

53020

Middle Eastern (MID)

AF:

0.168

AC:

965

AN:

5746

European-Non Finnish (NFE)

AF:

0.118

AC:

131302

AN:

1108804

Other (OTH)

AF:

0.158

AC:

9529

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

7292

14584

21877

29169

36461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4994

9988

14982

19976

24970

<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:

0.152

AC:

23035

AN:

151934

Hom.:

1968

Cov.:

AF XY:

0.156

AC XY:

11621

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.158

AC:

6557

AN:

41418

American (AMR)

AF:

0.139

AC:

2129

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

686

AN:

3466

East Asian (EAS)

AF:

0.407

AC:

2100

AN:

5166

South Asian (SAS)

AF:

0.201

AC:

970

AN:

4818

European-Finnish (FIN)

AF:

0.162

AC:

1700

AN:

10512

Middle Eastern (MID)

AF:

0.161

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.123

AC:

8388

AN:

67974

Other (OTH)

AF:

0.175

AC:

369

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

963

1925

2888

3850

4813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<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:

0.139

Hom.:

5975

Bravo

AF:

0.150

TwinsUK

AF:

0.115

AC:

426

ALSPAC

AF:

0.127

AC:

488

ESP6500AA

AF:

0.154

AC:

584

ESP6500EA

AF:

0.131

AC:

1081

ExAC

AF:

0.166

AC:

20042

Asia WGS

AF:

0.327

AC:

1134

AN:

3478

EpiCase

AF:

0.129

EpiControl

AF:

0.130

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Usher syndrome type 2C (3)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.79

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.1

PhyloP100

8.0

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-2.3

REVEL

Benign

0.22

Sift

Uncertain

0.010

Sift4G

Uncertain

0.0040

Polyphen

0.99

Vest4

0.32

MPC

0.34

ClinPred

0.033

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.48

gMVP

0.76

Mutation Taster

=80/20

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