rs375921325
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_032119.4(ADGRV1):c.6443C>T(p.Ala2148Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000498 in 1,605,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
ADGRV1
NM_032119.4 missense
NM_032119.4 missense
Scores
4
3
6
Clinical Significance
Conservation
PhyloP100: 5.90
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 Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.11524704).
BP6
?
Variant 5-90685948-C-T is Benign according to our data. Variant chr5-90685948-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 46353.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=1, Benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADGRV1 | NM_032119.4 | c.6443C>T | p.Ala2148Val | missense_variant | 29/90 | ENST00000405460.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADGRV1 | ENST00000405460.9 | c.6443C>T | p.Ala2148Val | missense_variant | 29/90 | 1 | NM_032119.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152118Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000696 AC: 17AN: 244092Hom.: 0 AF XY: 0.0000529 AC XY: 7AN XY: 132306
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GnomAD4 exome AF: 0.0000337 AC: 49AN: 1453250Hom.: 0 Cov.: 31 AF XY: 0.0000304 AC XY: 22AN XY: 722822
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 16, 2015 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 24, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2021 | The c.6443C>T (p.A2148V) alteration is located in exon 29 (coding exon 29) of the ADGRV1 gene. This alteration results from a C to T substitution at nucleotide position 6443, causing the alanine (A) at amino acid position 2148 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 19, 2013 | Ala2148Val in exon 29 of GPR98: This variant is not expected to have clinical si gnificance because it is has been identified in 3/3124 (0.09%) African American chromosomes from a broad population by the NHLBI Exome sequencing project (http: //evs.gs.washington.edu/EVS/) and due to a lack of conservation across species, including mammals. Of note, possum has a valine (Val) at this position despite h igh nearby amino acid conservation. In addition, this variant has now been ident ified in our laboratory in two individuals, neither of whom had a second GPR98 v ariant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
Polyphen
D;D;.
Vest4
0.47
MVP
0.76
MPC
0.32
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at