rs61753908

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.5953A>G(p.Asn1985Asp) variant causes a missense change. The variant allele was found at a frequency of 0.148 in 1,612,926 control chromosomes in the GnomAD database, including 21,177 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1985H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.20 ( 3734 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17443 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.02

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:

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=0.004298836).

BP6

Variant 5-90683874-A-G is Benign according to our data. Variant chr5-90683874-A-G is described in ClinVar as Benign. ClinVar VariationId is 46344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.391 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	NM_032119.4	MANE Select	c.5953A>G	p.Asn1985Asp	missense	Exon 28 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.6052A>G		non_coding_transcript_exon	Exon 28 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.5953A>G	p.Asn1985Asp	missense	Exon 28 of 90	ENSP00000384582.2
ADGRV1	ENST00000640403.1	TSL:5	c.3244A>G	p.Asn1082Asp	missense	Exon 18 of 29	ENSP00000492531.1
ADGRV1	ENST00000639473.1	TSL:5	n.1412A>G		non_coding_transcript_exon	Exon 8 of 23

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30455

AN:

151934

Hom.:

3717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.162

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.200

GnomAD2 exomes

AF:

0.180

AC:

44514

AN:

246954

AF XY:

0.177

show subpopulations

Gnomad AFR exome

AF:

0.332

Gnomad AMR exome

AF:

0.144

Gnomad ASJ exome

AF:

0.215

Gnomad EAS exome

AF:

0.411

Gnomad FIN exome

AF:

0.171

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.142

AC:

207758

AN:

1460874

Hom.:

17443

Cov.:

AF XY:

0.144

AC XY:

104475

AN XY:

726644

show subpopulations

African (AFR)

AF:

0.338

AC:

11300

AN:

33466

American (AMR)

AF:

0.147

AC:

6564

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.210

AC:

5495

AN:

26126

East Asian (EAS)

AF:

0.374

AC:

14825

AN:

39672

South Asian (SAS)

AF:

0.203

AC:

17465

AN:

86176

European-Finnish (FIN)

AF:

0.163

AC:

8686

AN:

53334

Middle Eastern (MID)

AF:

0.177

AC:

1020

AN:

5768

European-Non Finnish (NFE)

AF:

0.119

AC:

132034

AN:

1111404

Other (OTH)

AF:

0.172

AC:

10369

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

10549

21097

31646

42194

52743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5094

10188

15282

20376

25470

<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:

0.201

AC:

30504

AN:

152052

Hom.:

3734

Cov.:

AF XY:

0.204

AC XY:

15153

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.326

AC:

13495

AN:

41452

American (AMR)

AF:

0.162

AC:

2479

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

724

AN:

3464

East Asian (EAS)

AF:

0.406

AC:

2095

AN:

5162

South Asian (SAS)

AF:

0.209

AC:

1005

AN:

4816

European-Finnish (FIN)

AF:

0.162

AC:

1717

AN:

10580

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.124

AC:

8409

AN:

67986

Other (OTH)

AF:

0.208

AC:

439

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1189

2378

3568

4757

5946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.152

Hom.:

3148

Bravo

AF:

0.208

TwinsUK

AF:

0.116

AC:

430

ALSPAC

AF:

0.127

AC:

490

ESP6500AA

AF:

0.316

AC:

1176

ESP6500EA

AF:

0.132

AC:

1082

ExAC

AF:

0.182

AC:

22007

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Usher syndrome type 2C (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.042

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.94

PhyloP100

4.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.067

Sift

Benign

0.19

Sift4G

Benign

0.20

Polyphen

0.0030

Vest4

0.055

MPC

0.33

ClinPred

0.027

GERP RS

4.5

Varity_R

0.25

gMVP

0.45

Mutation Taster

=95/5

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over