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rs145294917

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS1

The NM_032119.4(ADGRV1):c.10796G>C(p.Gly3599Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000643 in 1,611,954 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00033 ( 7 hom. )

Consequence

ADGRV1
NM_032119.4 missense

Scores

1
1
10

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 5.22
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009105235).
BP6
Variant 5-90745617-G-C is Benign according to our data. Variant chr5-90745617-G-C is described in ClinVar as [Benign]. Clinvar id is 163596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-90745617-G-C is described in Lovd as [Benign]. Variant chr5-90745617-G-C is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00362 (551/152210) while in subpopulation AFR AF= 0.0121 (504/41538). AF 95% confidence interval is 0.0113. There are 1 homozygotes in gnomad4. There are 252 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADGRV1NM_032119.4 linkuse as main transcriptc.10796G>C p.Gly3599Ala missense_variant 52/90 ENST00000405460.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADGRV1ENST00000405460.9 linkuse as main transcriptc.10796G>C p.Gly3599Ala missense_variant 52/901 NM_032119.4 P1Q8WXG9-1

Frequencies

GnomAD3 genomes
AF:
0.00362
AC:
551
AN:
152092
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0122
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00269
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000898
AC:
223
AN:
248350
Hom.:
1
AF XY:
0.000601
AC XY:
81
AN XY:
134720
show subpopulations
Gnomad AFR exome
AF:
0.0131
Gnomad AMR exome
AF:
0.000377
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000328
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000355
Gnomad OTH exome
AF:
0.000499
GnomAD4 exome
AF:
0.000333
AC:
486
AN:
1459744
Hom.:
7
Cov.:
29
AF XY:
0.000267
AC XY:
194
AN XY:
726206
show subpopulations
Gnomad4 AFR exome
AF:
0.0120
Gnomad4 AMR exome
AF:
0.000470
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:
0.00000810
Gnomad4 OTH exome
AF:
0.000863
GnomAD4 genome
AF:
0.00362
AC:
551
AN:
152210
Hom.:
1
Cov.:
32
AF XY:
0.00339
AC XY:
252
AN XY:
74428
show subpopulations
Gnomad4 AFR
AF:
0.0121
Gnomad4 AMR
AF:
0.00268
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.000572
Hom.:
0
Bravo
AF:
0.00407
ESP6500AA
AF:
0.0131
AC:
48
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.00109
AC:
132
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingGeneDxDec 04, 2019- -
Likely benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 29, 2024- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineApr 30, 2012Gly3599Ala in Exon 52 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 1.4% (40/2958) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS; dbSNP rs145294917). -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
ADGRV1-related condition Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 24, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.39
Cadd
Benign
23
Dann
Uncertain
1.0
DEOGEN2
Benign
0.31
T;T
Eigen
Benign
0.18
Eigen_PC
Benign
0.20
FATHMM_MKL
Pathogenic
0.99
D
MetaRNN
Benign
0.0091
T;T
MetaSVM
Benign
-0.34
T
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.46
T
Polyphen
1.0
D;D
Vest4
0.64
MVP
0.66
MPC
0.34
ClinPred
0.058
T
GERP RS
4.1
Varity_R
0.42
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs145294917; hg19: chr5-90041434; API