rs61754947
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_032119.4(ADGRV1):āc.3295A>Gā(p.Thr1099Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000439 in 1,563,782 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.0023 ( 5 hom., cov: 32)
Exomes š: 0.00024 ( 2 hom. )
Consequence
ADGRV1
NM_032119.4 missense
NM_032119.4 missense
Scores
3
9
Clinical Significance
Conservation
PhyloP100: 6.10
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0076176524).
BP6
?
Variant 5-90651609-A-G is Benign according to our data. Variant chr5-90651609-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 226647.We mark this variant Likely_benign, oryginal submissions are: {Benign=5, Uncertain_significance=1}. Variant chr5-90651609-A-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0023 (350/152294) while in subpopulation AFR AF= 0.00821 (341/41558). AF 95% confidence interval is 0.00749. There are 5 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 5 AR,Digenic gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.3295A>G | p.Thr1099Ala | missense_variant | 18/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.3295A>G | p.Thr1099Ala | missense_variant | 18/90 | 1 | NM_032119.4 | P1 | |
ADGRV1 | ENST00000640403.1 | c.598A>G | p.Thr200Ala | missense_variant | 8/29 | 5 | |||
ADGRV1 | ENST00000504142.2 | n.2061A>G | non_coding_transcript_exon_variant | 12/14 | 5 | ||||
ADGRV1 | ENST00000639676.1 | n.893A>G | non_coding_transcript_exon_variant | 6/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00228 AC: 347AN: 152176Hom.: 5 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
347
AN:
152176
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000574 AC: 138AN: 240576Hom.: 3 AF XY: 0.000468 AC XY: 61AN XY: 130292
GnomAD3 exomes
AF:
AC:
138
AN:
240576
Hom.:
AF XY:
AC XY:
61
AN XY:
130292
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000238 AC: 336AN: 1411488Hom.: 2 Cov.: 25 AF XY: 0.000226 AC XY: 159AN XY: 703890
GnomAD4 exome
AF:
AC:
336
AN:
1411488
Hom.:
Cov.:
25
AF XY:
AC XY:
159
AN XY:
703890
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00230 AC: 350AN: 152294Hom.: 5 Cov.: 32 AF XY: 0.00216 AC XY: 161AN XY: 74470
GnomAD4 genome
?
AF:
AC:
350
AN:
152294
Hom.:
Cov.:
32
AF XY:
AC XY:
161
AN XY:
74470
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
25
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
85
Asia WGS
AF:
AC:
3
AN:
3472
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:7
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:5
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 23, 2018 | This 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. - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 24, 2018 | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 13, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 29, 2016 | Thr1099Ala in Exon 18 of GPR98: This variant is not expected to have clinical si gnificance because it has been identified in 1.0% (83/8572) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs61754947). - |
Usher syndrome type 2C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Benign
T
Polyphen
P;P;.
Vest4
0.69
MVP
0.60
MPC
0.19
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at