5-90685794-C-T

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.6289C>T(p.Arg2097Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,607,292 control chromosomes in the GnomAD database, including 537 homozygotes. In-silico tool predicts 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. R2097H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.036 ( 208 hom., cov: 31)

Exomes 𝑓: 0.014 ( 329 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 2.64

Publications

14 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=0.0022222996).

BP6

Variant 5-90685794-C-T is Benign according to our data. Variant chr5-90685794-C-T is described in ClinVar as Benign. ClinVar VariationId is 46350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0948 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.6289C>T	p.Arg2097Cys	missense	Exon 29 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.6388C>T		non_coding_transcript_exon	Exon 29 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.6289C>T	p.Arg2097Cys	missense	Exon 29 of 90	ENSP00000384582.2
ADGRV1	ENST00000640403.1	TSL:5	c.3580C>T	p.Arg1194Cys	missense	Exon 19 of 29	ENSP00000492531.1
ADGRV1	ENST00000639473.1	TSL:5	n.1748C>T		non_coding_transcript_exon	Exon 9 of 23

Frequencies

GnomAD3 genomes

AF:

0.0362

AC:

5506

AN:

151978

Hom.:

208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0973

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0178

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.00481

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.0283

GnomAD2 exomes

AF:

0.0182

AC:

4463

AN:

245222

AF XY:

0.0169

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0293

Gnomad EAS exome

AF:

0.0000558

Gnomad FIN exome

AF:

0.00660

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0210

GnomAD4 exome

AF:

0.0142

AC:

20699

AN:

1455196

Hom.:

329

Cov.:

AF XY:

0.0140

AC XY:

10102

AN XY:

724130

show subpopulations

African (AFR)

AF:

0.108

AC:

3616

AN:

33408

American (AMR)

AF:

0.0154

AC:

685

AN:

44566

Ashkenazi Jewish (ASJ)

AF:

0.0309

AC:

806

AN:

26046

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.0150

AC:

1284

AN:

85828

European-Finnish (FIN)

AF:

0.00696

AC:

349

AN:

50176

Middle Eastern (MID)

AF:

0.0471

AC:

271

AN:

5750

European-Non Finnish (NFE)

AF:

0.0114

AC:

12616

AN:

1109654

Other (OTH)

AF:

0.0178

AC:

1072

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

837

1674

2512

3349

4186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.0363

AC:

5515

AN:

152096

Hom.:

208

Cov.:

AF XY:

0.0353

AC XY:

2622

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0973

AC:

4035

AN:

41454

American (AMR)

AF:

0.0178

AC:

272

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0346

AC:

120

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0135

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00481

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0123

AC:

836

AN:

68000

Other (OTH)

AF:

0.0280

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

242

483

725

966

1208

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<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:

0.0197

Hom.:

260

Bravo

AF:

0.0409

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.102

AC:

378

ESP6500EA

AF:

0.0124

AC:

102

ExAC

AF:

0.0200

AC:

2411

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0138

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

not provided (1)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.2

PhyloP100

2.6

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-4.8

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.15

MPC

0.36

ClinPred

0.020

GERP RS

3.1

Varity_R

0.46

gMVP

0.65

Mutation Taster

=83/17

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over