rs2438378

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.16279G>A(p.Val5427Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.995 in 1,613,940 control chromosomes in the GnomAD database, including 798,880 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 Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V5427E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.97 ( 72243 hom., cov: 32)

Exomes 𝑓: 1.0 ( 726637 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.120

Publications

32 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: Orphanet, ClinGen
Usher syndrome type 2C
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
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=6.644323E-7).

BP6

Variant 5-90823507-G-A is Benign according to our data. Variant chr5-90823507-G-A is described in ClinVar as Benign. ClinVar VariationId is 46285.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 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.16279G>A	p.Val5427Met	missense	Exon 76 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.16295G>A		non_coding_transcript_exon	Exon 76 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.16279G>A	p.Val5427Met	missense	Exon 76 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000638510.1	TSL:1	n.3546G>A		non_coding_transcript_exon	Exon 12 of 26
ADGRV1	ENST00000425867.3	TSL:5	c.5233G>A	p.Val1745Met	missense	Exon 24 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes

AF:

0.973

AC:

148114

AN:

152156

Hom.:

72197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.911

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.986

Gnomad ASJ

AF:

0.995

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.984

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.970

GnomAD2 exomes

AF:

0.993

AC:

247487

AN:

249218

AF XY:

0.995

show subpopulations

Gnomad AFR exome

AF:

0.908

Gnomad AMR exome

AF:

0.995

Gnomad ASJ exome

AF:

0.997

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.994

GnomAD4 exome

AF:

0.997

AC:

1457301

AN:

1461666

Hom.:

726637

Cov.:

AF XY:

0.997

AC XY:

725234

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.906

AC:

30342

AN:

33478

American (AMR)

AF:

0.994

AC:

44464

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.996

AC:

26034

AN:

26132

East Asian (EAS)

AF:

1.00

AC:

39692

AN:

39692

South Asian (SAS)

AF:

1.00

AC:

86226

AN:

86254

European-Finnish (FIN)

AF:

1.00

AC:

53401

AN:

53402

Middle Eastern (MID)

AF:

0.991

AC:

5713

AN:

5766

European-Non Finnish (NFE)

AF:

1.00

AC:

1111494

AN:

1111848

Other (OTH)

AF:

0.993

AC:

59935

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

216

432

648

864

1080

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21668

43336

65004

86672

108340

<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:

0.973

AC:

148217

AN:

152274

Hom.:

72243

Cov.:

AF XY:

0.974

AC XY:

72526

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.911

AC:

37817

AN:

41530

American (AMR)

AF:

0.986

AC:

15082

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.995

AC:

3455

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5180

AN:

5180

South Asian (SAS)

AF:

0.999

AC:

4818

AN:

4822

European-Finnish (FIN)

AF:

1.00

AC:

10622

AN:

10622

Middle Eastern (MID)

AF:

0.983

AC:

289

AN:

294

European-Non Finnish (NFE)

AF:

0.999

AC:

67991

AN:

68038

Other (OTH)

AF:

0.970

AC:

2051

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

194

388

582

776

970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

914

1828

2742

3656

4570

<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:

0.990

Hom.:

188937

Bravo

AF:

0.970

TwinsUK

AF:

1.00

AC:

3707

ALSPAC

AF:

0.999

AC:

3852

ESP6500AA

AF:

0.914

AC:

3541

ESP6500EA

AF:

0.999

AC:

8270

ExAC

AF:

0.992

AC:

119849

Asia WGS

AF:

0.997

AC:

3466

AN:

3478

EpiCase

AF:

1.00

EpiControl

AF:

0.999

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

not provided (2)

Usher syndrome type 2C (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.083

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.067

Eigen

Benign

-2.3

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.071

MetaRNN

Benign

6.6e-7

MetaSVM

Benign

-0.98

PhyloP100

-0.12

PrimateAI

Benign

0.21

PROVEAN

Benign

0.33

REVEL

Benign

0.093

Sift

Benign

0.30

Sift4G

Benign

0.26

Polyphen

0.0010

Vest4

0.056

MPC

0.048

ClinPred

0.015

GERP RS

-9.7

Varity_R

0.020

gMVP

0.31

Mutation Taster

=99/1

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

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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