rs2438374

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.16031A>G(p.Glu5344Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.97 in 1,612,382 control chromosomes in the GnomAD database, including 759,533 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E5344V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.94 ( 67407 hom., cov: 33)

Exomes 𝑓: 0.97 ( 692126 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.71

Publications

37 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=7.7724985E-7).

BP6

Variant 5-90811291-A-G is Benign according to our data. Variant chr5-90811291-A-G is described in ClinVar as Benign. ClinVar VariationId is 46282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.16031A>G	p.Glu5344Gly	missense	Exon 74 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.16047A>G		non_coding_transcript_exon	Exon 74 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.16031A>G	p.Glu5344Gly	missense	Exon 74 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000638510.1	TSL:1	n.3298A>G		non_coding_transcript_exon	Exon 10 of 26
ADGRV1	ENST00000425867.3	TSL:5	c.4985A>G	p.Glu1662Gly	missense	Exon 22 of 38	ENSP00000392618.3	A0A1X7SBU6

Frequencies

GnomAD3 genomes

AF:

0.939

AC:

142915

AN:

152140

Hom.:

67375

Cov.:

show subpopulations

Gnomad AFR

AF:

0.847

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.962

Gnomad ASJ

AF:

0.918

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.993

Gnomad FIN

AF:

0.982

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.976

Gnomad OTH

AF:

0.936

GnomAD2 exomes

AF:

0.970

AC:

238719

AN:

246210

AF XY:

0.972

show subpopulations

Gnomad AFR exome

AF:

0.846

Gnomad AMR exome

AF:

0.980

Gnomad ASJ exome

AF:

0.923

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.981

Gnomad NFE exome

AF:

0.974

Gnomad OTH exome

AF:

0.969

GnomAD4 exome

AF:

0.973

AC:

1421241

AN:

1460124

Hom.:

692126

Cov.:

AF XY:

0.974

AC XY:

707375

AN XY:

726148

show subpopulations

African (AFR)

AF:

0.843

AC:

28195

AN:

33436

American (AMR)

AF:

0.977

AC:

43516

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.923

AC:

24079

AN:

26076

East Asian (EAS)

AF:

1.00

AC:

39694

AN:

39694

South Asian (SAS)

AF:

0.994

AC:

85183

AN:

85732

European-Finnish (FIN)

AF:

0.982

AC:

52412

AN:

53384

Middle Eastern (MID)

AF:

0.960

AC:

5531

AN:

5760

European-Non Finnish (NFE)

AF:

0.976

AC:

1084415

AN:

1111150

Other (OTH)

AF:

0.965

AC:

58216

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

1746

3492

5239

6985

8731

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21642

43284

64926

86568

108210

<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:

0.939

AC:

143001

AN:

152258

Hom.:

67407

Cov.:

AF XY:

0.941

AC XY:

70051

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.847

AC:

35146

AN:

41512

American (AMR)

AF:

0.962

AC:

14714

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.918

AC:

3184

AN:

3470

East Asian (EAS)

AF:

1.00

AC:

5181

AN:

5182

South Asian (SAS)

AF:

0.993

AC:

4796

AN:

4828

European-Finnish (FIN)

AF:

0.982

AC:

10424

AN:

10618

Middle Eastern (MID)

AF:

0.952

AC:

280

AN:

294

European-Non Finnish (NFE)

AF:

0.976

AC:

66382

AN:

68036

Other (OTH)

AF:

0.937

AC:

1982

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

421

843

1264

1686

2107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.959

Hom.:

159013

Bravo

AF:

0.932

TwinsUK

AF:

0.971

AC:

3599

ALSPAC

AF:

0.975

AC:

3758

ESP6500AA

AF:

0.854

AC:

3209

ESP6500EA

AF:

0.973

AC:

8017

ExAC

AF:

0.968

AC:

116947

Asia WGS

AF:

0.987

AC:

3433

AN:

3478

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

0.038

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.76

CADD

Benign

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.071

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.036

MetaRNN

Benign

7.8e-7

MetaSVM

Benign

-0.97

PhyloP100

1.7

PrimateAI

Benign

0.33

PROVEAN

Benign

1.9

REVEL

Benign

0.070

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.065

MPC

0.053

ClinPred

0.0024

GERP RS

4.6

Varity_R

0.060

gMVP

0.52

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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