7-1057919-G-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001303473.2(GPR146):c.404G>A(p.Arg135Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 774,898 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0018 ( 11 hom. )
Consequence
GPR146
NM_001303473.2 missense
NM_001303473.2 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 9.21
Genes affected
GPR146 (HGNC:21718): (G protein-coupled receptor 146) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.013405383).
BP6
Variant 7-1057919-G-A is Benign according to our data. Variant chr7-1057919-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657177.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 11 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GPR146 | NM_001303473.2 | c.404G>A | p.Arg135Gln | missense_variant | 2/2 | ENST00000444847.2 | NP_001290402.1 | |
C7orf50 | NM_001318252.2 | c.130-47776C>T | intron_variant | ENST00000397098.8 | NP_001305181.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GPR146 | ENST00000444847.2 | c.404G>A | p.Arg135Gln | missense_variant | 2/2 | 2 | NM_001303473.2 | ENSP00000410743 | P1 | |
C7orf50 | ENST00000397098.8 | c.130-47776C>T | intron_variant | 1 | NM_001318252.2 | ENSP00000380286 | P1 | |||
ENST00000549241.1 | n.1343C>T | non_coding_transcript_exon_variant | 1/2 | 4 |
Frequencies
GnomAD3 genomes AF: 0.00108 AC: 165AN: 152228Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00171 AC: 422AN: 246410Hom.: 3 AF XY: 0.00215 AC XY: 288AN XY: 133852
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GnomAD4 exome AF: 0.00184 AC: 1146AN: 622552Hom.: 11 Cov.: 0 AF XY: 0.00220 AC XY: 747AN XY: 339782
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GnomAD4 genome AF: 0.00108 AC: 165AN: 152346Hom.: 0 Cov.: 33 AF XY: 0.00102 AC XY: 76AN XY: 74490
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | GPR146: BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
.;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
D;D
Sift4G
Pathogenic
D;D
Polyphen
1.0
.;D
Vest4
0.90
MVP
MPC
0.46
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T
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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