rs199833843

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The ENST00000405460.9(ADGRV1):ā€‹c.9635T>Cā€‹(p.Ile3212Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000962 in 1,610,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I3212V) has been classified as Likely benign.

Frequency

Genomes: š‘“ 0.00053 ( 0 hom., cov: 32)
Exomes š‘“: 0.000051 ( 0 hom. )

Consequence

ADGRV1
ENST00000405460.9 missense

Scores

1
17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: 7.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.012087733).
BP6
Variant 5-90720946-T-C is Benign according to our data. Variant chr5-90720946-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 290825.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2, Likely_benign=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADGRV1NM_032119.4 linkuse as main transcriptc.9635T>C p.Ile3212Thr missense_variant 45/90 ENST00000405460.9 NP_115495.3
LOC105379077XR_001742802.2 linkuse as main transcriptn.364-5137A>G intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADGRV1ENST00000405460.9 linkuse as main transcriptc.9635T>C p.Ile3212Thr missense_variant 45/901 NM_032119.4 ENSP00000384582 P1Q8WXG9-1

Frequencies

GnomAD3 genomes
AF:
0.000519
AC:
79
AN:
152206
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00174
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
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:
0.000956
GnomAD3 exomes
AF:
0.000117
AC:
29
AN:
248458
Hom.:
0
AF XY:
0.000111
AC XY:
15
AN XY:
134794
show subpopulations
Gnomad AFR exome
AF:
0.00175
Gnomad AMR exome
AF:
0.0000292
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:
0.00
Gnomad OTH exome
AF:
0.000166
GnomAD4 exome
AF:
0.0000514
AC:
75
AN:
1458202
Hom.:
0
Cov.:
29
AF XY:
0.0000469
AC XY:
34
AN XY:
725452
show subpopulations
Gnomad4 AFR exome
AF:
0.00177
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000525
AC:
80
AN:
152324
Hom.:
0
Cov.:
32
AF XY:
0.000537
AC XY:
40
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00176
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.0000630
Hom.:
0
Bravo
AF:
0.000627
ESP6500AA
AF:
0.00158
AC:
6
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000141
AC:
17
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxMay 12, 2018This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Sep 12, 2016- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 17, 2024- -
Febrile seizures, familial, 4;C2931213:Usher syndrome type 2C Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsOct 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
18
DANN
Benign
0.84
DEOGEN2
Benign
0.12
T;T
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.17
FATHMM_MKL
Benign
0.64
D
LIST_S2
Benign
0.61
.;T
M_CAP
Benign
0.060
D
MetaRNN
Benign
0.012
T;T
MetaSVM
Benign
-0.73
T
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-2.0
.;N
REVEL
Benign
0.048
Sift
Benign
0.072
.;T
Sift4G
Uncertain
0.015
.;D
Polyphen
0.094
B;B
Vest4
0.18
MVP
0.50
MPC
0.063
ClinPred
0.070
T
GERP RS
5.8
Varity_R
0.14
gMVP
0.43

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.

Other links and lift over

dbSNP: rs199833843; hg19: chr5-90016763; API