rs10067636

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.10039T>C(p.Phe3347Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0035 in 1,461,344 control chromosomes in the GnomAD database, including 146 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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.

Frequency

Genomes: 𝑓 0.019 ( 84 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 62 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.313

Publications

5 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:

LOC105379077 (HGNC:):

LOC105379077 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=0.0014689565).

BP6

Variant 5-90725218-T-C is Benign according to our data. Variant chr5-90725218-T-C is described in ClinVar as Benign. ClinVar VariationId is 46244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0656 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.10039T>C	p.Phe3347Leu	missense	Exon 47 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.10055T>C		non_coding_transcript_exon	Exon 47 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.10039T>C	p.Phe3347Leu	missense	Exon 47 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000509621.1	TSL:1	n.2736T>C		non_coding_transcript_exon	Exon 15 of 26
ADGRV1	ENST00000640374.1	TSL:5	n.3183T>C		non_coding_transcript_exon	Exon 17 of 27

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2954

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0677

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

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:

0.00548

AC:

783

AN:

142846

AF XY:

0.00427

show subpopulations

Gnomad AFR exome

AF:

0.0737

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.00165

AC:

2158

AN:

1309080

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

954

AN XY:

650622

show subpopulations

African (AFR)

AF:

0.0622

AC:

1710

AN:

27476

American (AMR)

AF:

0.00428

AC:

AN:

20576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22326

East Asian (EAS)

AF:

0.00

AC:

AN:

36266

South Asian (SAS)

AF:

0.000116

AC:

AN:

68872

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50516

Middle Eastern (MID)

AF:

0.00118

AC:

AN:

5106

European-Non Finnish (NFE)

AF:

0.000140

AC:

143

AN:

1023706

Other (OTH)

AF:

0.00374

AC:

203

AN:

54236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

192

287

383

479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0194

AC:

2959

AN:

152264

Hom.:

Cov.:

AF XY:

0.0186

AC XY:

1382

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0677

AC:

2813

AN:

41558

American (AMR)

AF:

0.00673

AC:

103

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67990

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

141

283

424

566

707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0105

Hom.:

Bravo

AF:

0.0217

ESP6500AA

AF:

0.0623

AC:

222

ESP6500EA

AF:

0.000250

AC:

ExAC

AF:

0.00531

AC:

629

Asia WGS

AF:

0.00407

AC:

AN:

3454

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.55

DEOGEN2

Benign

0.072

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.47

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.98

PhyloP100

-0.31

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.28

REVEL

Benign

0.021

Sift

Benign

0.59

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.061

MutPred

0.30

Loss of methylation at K3348 (P = 0.0285)

MVP

0.10

MPC

0.053

ClinPred

0.0025

GERP RS

0.88

Varity_R

0.056

gMVP

0.38

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over