Variant 5-90653530-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP3BP6_Moderate

The NM_032119.4(ADGRV1):c.3956G>C(p.Arg1319Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,634 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1319Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.64

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 links:

ADGRV1 (HGNC:):

ADGRV1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.796

BP6

Variant 5-90653530-G-C is Benign according to our data. Variant chr5-90653530-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2112499.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.3956G>C	p.Arg1319Pro	missense_variant	20/90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRV1	ENST00000405460.9 linkuse as main transcript	c.3956G>C	p.Arg1319Pro	missense_variant	20/90	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000640403.1 linkuse as main transcript	c.1247G>C	p.Arg416Pro	missense_variant	10/29	5		ENSP00000492531.1	A0A1W2PRC7
ADGRV1	ENST00000504142.2 linkuse as main transcript	n.2722G>C		non_coding_transcript_exon_variant	14/14	5
ADGRV1	ENST00000639676.1 linkuse as main transcript	n.1554G>C		non_coding_transcript_exon_variant	8/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248940

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

135040

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461634

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.032

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;.

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.80

D;D;D

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.7

.;D;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0090

.;D;.

Sift4G

Pathogenic

0.0

.;D;.

Polyphen

1.0

D;D;.

Vest4

0.88

MutPred

0.42

Loss of catalytic residue at R1319 (P = 0.0109);Loss of catalytic residue at R1319 (P = 0.0109);.;

MVP

0.74

MPC

0.32

ClinPred

0.98

GERP RS

5.4

Varity_R

0.87

gMVP

0.95

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over