rs2454727
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong
The NM_177551.4(HCAR2):c.951G>A(p.Met317Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.
Frequency
Genomes: 𝑓 0.23 ( 3 hom., cov: 32)
Exomes 𝑓: 0.12 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
HCAR2
NM_177551.4 missense
NM_177551.4 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: -4.12
Genes affected
HCAR2 (HGNC:24827): (hydroxycarboxylic acid receptor 2) Predicted to enable nicotinic acid receptor activity. Involved in neutrophil apoptotic process and positive regulation of neutrophil apoptotic process. Located in cell junction and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0018282831).
BP6
?
Variant 12-122702333-C-T is Benign according to our data. Variant chr12-122702333-C-T is described in ClinVar as [Benign]. Clinvar id is 770415.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HCAR2 | NM_177551.4 | c.951G>A | p.Met317Ile | missense_variant | 1/1 | ENST00000328880.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HCAR2 | ENST00000328880.6 | c.951G>A | p.Met317Ile | missense_variant | 1/1 | NM_177551.4 | P1 | ||
ENST00000543611.1 | n.401+1003C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 33186AN: 145294Hom.: 3 Cov.: 32 FAILED QC
GnomAD3 genomes
?
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32
FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.121 AC: 140790AN: 1166210Hom.: 1 Cov.: 42 AF XY: 0.124 AC XY: 72600AN XY: 583724
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.228 AC: 33180AN: 145410Hom.: 3 Cov.: 32 AF XY: 0.224 AC XY: 15850AN XY: 70798
GnomAD4 genome
?
Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 13, 2018 | This variant is associated with the following publications: (PMID: 25363768) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Mar 28, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
P;P
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of methylation at K316 (P = 0.024);
MPC
ClinPred
T
GERP RS
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