NM_032119.4:c.2023A>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_032119.4(ADGRV1):c.2023A>C(p.Ile675Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,605,308 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000096 ( 1 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: 2.40

Publications

2 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005372584).

BP6

Variant 5-90637731-A-C is Benign according to our data. Variant chr5-90637731-A-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 227402.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00123 (187/152320) while in subpopulation AFR AF = 0.0038 (158/41582). AF 95% confidence interval is 0.00332. There are 1 homozygotes in GnomAd4. There are 85 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.2023A>C	p.Ile675Leu	missense	Exon 11 of 90	NP_115495.3	Q8WXG9-1
	ADGRV1	NR_003149.2		n.2122A>C		non_coding_transcript_exon	Exon 11 of 90

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADGRV1	ENST00000405460.9	TSL:1 MANE Select	c.2023A>C	p.Ile675Leu	missense	Exon 11 of 90	ENSP00000384582.2	Q8WXG9-1
	ADGRV1	ENST00000504142.2	TSL:5	n.789A>C		non_coding_transcript_exon	Exon 5 of 14

Frequencies

GnomAD3 genomes

AF:

0.00121

AC:

184

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00374

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000288

AC:

AN:

243164

AF XY:

0.000235

show subpopulations

Gnomad AFR exome

AF:

0.00426

Gnomad AMR exome

AF:

0.0000899

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000905

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000964

AC:

140

AN:

1452988

Hom.:

Cov.:

AF XY:

0.0000789

AC XY:

AN XY:

722856

show subpopulations

African (AFR)

AF:

0.00336

AC:

111

AN:

33070

American (AMR)

AF:

0.000229

AC:

AN:

43680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25882

East Asian (EAS)

AF:

0.00

AC:

AN:

39608

South Asian (SAS)

AF:

0.00

AC:

AN:

84894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53010

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107102

Other (OTH)

AF:

0.000283

AC:

AN:

60020

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.00123

AC:

187

AN:

152320

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00380

AC:

158

AN:

41582

American (AMR)

AF:

0.00170

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68038

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000509

Hom.:

Bravo

AF:

0.00155

ESP6500AA

AF:

0.00333

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000298

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (2)

ADGRV1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.086

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.080

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.53

M_CAP

Benign

0.017

MetaRNN

Benign

0.0054

MetaSVM

Benign

-1.1

PhyloP100

2.4

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.23

REVEL

Benign

0.042

Sift

Benign

0.41

Sift4G

Benign

0.40

Polyphen

0.028

Vest4

0.45

MVP

0.36

MPC

0.066

ClinPred

0.0090

GERP RS

4.7

Varity_R

0.095

gMVP

0.55

Mutation Taster

=76/24

polymorphism

(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