5-90704393-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.8291C>T(p.Ser2764Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0612 in 1,553,964 control chromosomes in the GnomAD database, including 3,387 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. S2764W) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.053 ( 308 hom., cov: 32)

Exomes 𝑓: 0.062 ( 3079 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.01

Publications

29 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=0.0017643273).

BP6

Variant 5-90704393-C-T is Benign according to our data. Variant chr5-90704393-C-T is described in ClinVar as Benign. ClinVar VariationId is 46387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 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.8291C>T	p.Ser2764Leu	missense	Exon 36 of 90	NP_115495.3
	ADGRV1	NR_003149.2		n.8307C>T		non_coding_transcript_exon	Exon 36 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.8291C>T	p.Ser2764Leu	missense	Exon 36 of 90	ENSP00000384582.2
ADGRV1	ENST00000509621.1	TSL:1	n.988C>T		non_coding_transcript_exon	Exon 4 of 26
ADGRV1	ENST00000640403.1	TSL:5	c.5582C>T	p.Ser1861Leu	missense	Exon 26 of 29	ENSP00000492531.1

Frequencies

GnomAD3 genomes

AF:

0.0527

AC:

8012

AN:

152016

Hom.:

306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0116

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0447

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.118

Gnomad SAS

AF:

0.0931

Gnomad FIN

AF:

0.0949

Gnomad MID

AF:

0.0414

Gnomad NFE

AF:

0.0658

Gnomad OTH

AF:

0.0603

GnomAD2 exomes

AF:

0.0617

AC:

11696

AN:

189596

AF XY:

0.0631

show subpopulations

Gnomad AFR exome

AF:

0.00838

Gnomad AMR exome

AF:

0.0291

Gnomad ASJ exome

AF:

0.0423

Gnomad EAS exome

AF:

0.0903

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0630

Gnomad OTH exome

AF:

0.0599

GnomAD4 exome

AF:

0.0621

AC:

87032

AN:

1401830

Hom.:

3079

Cov.:

AF XY:

0.0629

AC XY:

43641

AN XY:

693516

show subpopulations

African (AFR)

AF:

0.00861

AC:

279

AN:

32418

American (AMR)

AF:

0.0316

AC:

1224

AN:

38764

Ashkenazi Jewish (ASJ)

AF:

0.0398

AC:

1008

AN:

25342

East Asian (EAS)

AF:

0.127

AC:

4790

AN:

37754

South Asian (SAS)

AF:

0.0815

AC:

6388

AN:

78356

European-Finnish (FIN)

AF:

0.0958

AC:

4890

AN:

51062

Middle Eastern (MID)

AF:

0.0491

AC:

279

AN:

5684

European-Non Finnish (NFE)

AF:

0.0602

AC:

64632

AN:

1074072

Other (OTH)

AF:

0.0607

AC:

3542

AN:

58378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

3394

6787

10181

13574

16968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2358

4716

7074

9432

11790

<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:

0.0527

AC:

8019

AN:

152134

Hom.:

308

Cov.:

AF XY:

0.0549

AC XY:

4079

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0115

AC:

479

AN:

41538

American (AMR)

AF:

0.0446

AC:

682

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0392

AC:

136

AN:

3468

East Asian (EAS)

AF:

0.119

AC:

615

AN:

5176

South Asian (SAS)

AF:

0.0936

AC:

451

AN:

4818

European-Finnish (FIN)

AF:

0.0949

AC:

1001

AN:

10550

Middle Eastern (MID)

AF:

0.0445

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0658

AC:

4475

AN:

67990

Other (OTH)

AF:

0.0601

AC:

127

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

381

763

1144

1526

1907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0595

Hom.:

1013

Bravo

AF:

0.0455

TwinsUK

AF:

0.0574

AC:

213

ALSPAC

AF:

0.0669

AC:

258

ESP6500AA

AF:

0.0116

AC:

ESP6500EA

AF:

0.0611

AC:

501

ExAC

AF:

0.0470

AC:

5608

Asia WGS

AF:

0.112

AC:

390

AN:

3476

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (1)

Usher syndrome type 2C (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.13

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0018

MetaSVM

Benign

-1.1

PhyloP100

1.0

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

REVEL

Benign

0.031

Sift

Benign

0.28

Sift4G

Benign

0.57

Polyphen

0.0030

Vest4

0.042

MPC

0.044

ClinPred

0.0079

GERP RS

3.1

Varity_R

0.12

gMVP

0.38

Mutation Taster

=92/8

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over