chr5-90683933-G-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.6012G>T(p.Leu2004Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,170 control chromosomes in the GnomAD database, including 27,053 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5520 hom., cov: 32)

Exomes 𝑓: 0.16 ( 21533 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.27

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=0.0043822527).

BP6

Variant 5-90683933-G-T is Benign according to our data. Variant chr5-90683933-G-T is described in ClinVar as Benign. ClinVar VariationId is 46346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 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.6012G>T	p.Leu2004Phe	missense	Exon 28 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.6111G>T		non_coding_transcript_exon	Exon 28 of 90

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.6012G>T	p.Leu2004Phe	missense	Exon 28 of 90	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000640403.1	TSL:5	c.3303G>T	p.Leu1101Phe	missense	Exon 18 of 29	ENSP00000492531.1	A0A1W2PRC7
ADGRV1	ENST00000639473.1	TSL:5	n.1471G>T		non_coding_transcript_exon	Exon 8 of 23

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36050

AN:

151864

Hom.:

5498

Cov.:

show subpopulations

Gnomad AFR

AF:

0.426

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.405

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.167

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.229

GnomAD2 exomes

AF:

0.198

AC:

49141

AN:

247808

AF XY:

0.194

show subpopulations

Gnomad AFR exome

AF:

0.437

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.409

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.157

AC:

228788

AN:

1461188

Hom.:

21533

Cov.:

AF XY:

0.158

AC XY:

114721

AN XY:

726816

show subpopulations

African (AFR)

AF:

0.450

AC:

15066

AN:

33474

American (AMR)

AF:

0.163

AC:

7276

AN:

44668

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

6307

AN:

26128

East Asian (EAS)

AF:

0.374

AC:

14823

AN:

39680

South Asian (SAS)

AF:

0.218

AC:

18771

AN:

86220

European-Finnish (FIN)

AF:

0.170

AC:

9057

AN:

53358

Middle Eastern (MID)

AF:

0.224

AC:

1294

AN:

5768

European-Non Finnish (NFE)

AF:

0.130

AC:

144724

AN:

1111540

Other (OTH)

AF:

0.190

AC:

11470

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

11408

22815

34223

45630

57038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5560

11120

16680

22240

27800

<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:

0.238

AC:

36110

AN:

151982

Hom.:

5520

Cov.:

AF XY:

0.240

AC XY:

17796

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.426

AC:

17633

AN:

41410

American (AMR)

AF:

0.180

AC:

2752

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

845

AN:

3466

East Asian (EAS)

AF:

0.406

AC:

2090

AN:

5152

South Asian (SAS)

AF:

0.222

AC:

1069

AN:

4820

European-Finnish (FIN)

AF:

0.167

AC:

1759

AN:

10554

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.136

AC:

9245

AN:

67986

Other (OTH)

AF:

0.236

AC:

499

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1267

2533

3800

5066

6333

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.174

Hom.:

11108

Bravo

AF:

0.250

TwinsUK

AF:

0.126

AC:

466

ALSPAC

AF:

0.138

AC:

533

ESP6500AA

AF:

0.418

AC:

1557

ESP6500EA

AF:

0.144

AC:

1183

ExAC

AF:

0.203

AC:

24458

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Usher syndrome type 2C (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.18

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.87

MetaRNN

Benign

0.0044

MetaSVM

Benign

-0.92

PhyloP100

1.3

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

REVEL

Benign

0.19

Sift

Benign

0.043

Sift4G

Uncertain

0.048

Polyphen

1.0

Vest4

0.084

MutPred

0.56

Gain of methylation at K2005 (P = 0.0283)

MPC

0.33

ClinPred

0.035

GERP RS

3.5

Varity_R

0.27

gMVP

0.38

Mutation Taster

=82/18

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

Computational scores

Splicing

Publications

Other links and lift over