Variant rs371781264 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_032119.4(ADGRV1):c.1466C>T(p.Pro489Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,688 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.78

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:

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;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADGRV1	NM_032119.4 link	c.1466C>T	p.Pro489Leu	missense_variant	8/90	ENST00000405460.9	NP_115495.3	Q8WXG9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ADGRV1	ENST00000405460.9 link	c.1466C>T	p.Pro489Leu	missense_variant	8/90	1	NM_032119.4	ENSP00000384582.2	Q8WXG9-1
ADGRV1	ENST00000504142.2 link	n.232C>T		non_coding_transcript_exon_variant	2/14	5
ADGRV1	ENST00000640083.1 link	n.1171C>T		non_coding_transcript_exon_variant	6/6	5
ADGRV1	ENST00000640109.1 link	n.1562C>T		non_coding_transcript_exon_variant	8/9	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

249022

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135082

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727126

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.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

May 16, 2017

The p.Pro489Leu variant in GPR98 has not been previously reported in individuals with hearing loss, but has been identified in 2/111492 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSN P rs371781264). Although this variant has been seen in the general population, i ts frequency is not high enough to rule out a pathogenic role. Computational pre diction tools and conservation analysis do not provide strong support for or aga inst an impact to the protein. In summary, the clinical significance of the p.Pr o489Leu variant is uncertain. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.84

.;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.53

D;D

MetaSVM

Benign

-0.80

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.4

.;D

REVEL

Benign

0.29

Sift

Uncertain

0.0030

.;D

Sift4G

Uncertain

0.0090

.;D

Polyphen

0.98

D;D

Vest4

0.47

MVP

0.69

MPC

0.29

ClinPred

0.98

GERP RS

5.2

Varity_R

0.20

gMVP

0.60

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