rs111033430

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.7229A>G(p.Tyr2410Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00378 in 1,613,360 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 98 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 91 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.21

Publications

9 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=0.0042912364).

BP6

Variant 5-90693985-A-G is Benign according to our data. Variant chr5-90693985-A-G is described in ClinVar as Benign. ClinVar VariationId is 46366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0697 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.7229A>G	p.Tyr2410Cys	missense	Exon 33 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.7245A>G		non_coding_transcript_exon	Exon 33 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.7229A>G	p.Tyr2410Cys	missense	Exon 33 of 90	ENSP00000384582.2
ADGRV1	ENST00000640403.1	TSL:5	c.4520A>G	p.Tyr1507Cys	missense	Exon 23 of 29	ENSP00000492531.1
ADGRV1	ENST00000639473.1	TSL:5	n.2688A>G		non_coding_transcript_exon	Exon 13 of 23

Frequencies

GnomAD3 genomes

AF:

0.0206

AC:

3128

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.00496

AC:

1231

AN:

248140

AF XY:

0.00392

show subpopulations

Gnomad AFR exome

AF:

0.0708

Gnomad AMR exome

AF:

0.00300

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000196

Gnomad OTH exome

AF:

0.00150

GnomAD4 exome

AF:

0.00203

AC:

2962

AN:

1461084

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1271

AN XY:

726788

show subpopulations

African (AFR)

AF:

0.0699

AC:

2339

AN:

33466

American (AMR)

AF:

0.00368

AC:

164

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.000162

AC:

AN:

86182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000153

AC:

170

AN:

1111588

Other (OTH)

AF:

0.00438

AC:

264

AN:

60334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

172

344

517

689

861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0206

AC:

3136

AN:

152276

Hom.:

Cov.:

AF XY:

0.0196

AC XY:

1461

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.0719

AC:

2988

AN:

41560

American (AMR)

AF:

0.00687

AC:

105

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68028

Other (OTH)

AF:

0.0118

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

153

306

459

612

765

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00684

Hom.:

Bravo

AF:

0.0229

ESP6500AA

AF:

0.0691

AC:

262

ESP6500EA

AF:

0.000243

AC:

ExAC

AF:

0.00604

AC:

730

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (5)

not specified (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

0.20

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.83

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.1

PhyloP100

2.2

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.1

REVEL

Benign

0.20

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.32

MVP

0.73

MPC

0.33

ClinPred

0.032

GERP RS

3.5

Varity_R

0.40

gMVP

0.74

Mutation Taster

=56/44

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