Variant rs188772875 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_032119.4(ADGRV1):c.3509A>C(p.Tyr1170Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,166 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.10

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 5-90652438-A-C is Pathogenic according to our data. Variant chr5-90652438-A-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1217227.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.19179848). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 linkuse as main transcript	c.3509A>C	p.Tyr1170Ser	missense_variant	19/90	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.3509A>C	p.Tyr1170Ser	missense_variant	19/90	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000640403.1 linkuse as main transcript	c.812A>C	p.Tyr271Ser	missense_variant	9/29	5		ENSP00000492531.1	A0A1W2PRC7
ADGRV1	ENST00000504142.2 linkuse as main transcript	n.2275A>C		non_coding_transcript_exon_variant	13/14	5
ADGRV1	ENST00000639676.1 linkuse as main transcript	n.1107A>C		non_coding_transcript_exon_variant	7/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249074

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135106

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461166

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726834

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Idiopathic generalized epilepsy

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Paris Brain Institute, Inserm - ICM

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.074

T;T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.78

.;T;T

M_CAP

Benign

0.059

MetaRNN

Benign

0.19

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.5

.;N;.

REVEL

Benign

0.13

Sift

Benign

0.17

.;T;.

Sift4G

Benign

0.065

.;T;.

Polyphen

0.76

P;P;.

Vest4

0.28

MutPred

0.43

Gain of disorder (P = 0.0051);Gain of disorder (P = 0.0051);.;

MVP

0.62

MPC

0.079

ClinPred

0.34

GERP RS

6.1

Varity_R

0.18

gMVP

0.53

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

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