chr2-233942727-C-G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2
The NM_024080.5(TRPM8):c.678C>G(p.Leu226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,614,156 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0052 ( 10 hom., cov: 31)
Exomes 𝑓: 0.00075 ( 11 hom. )
Consequence
TRPM8
NM_024080.5 synonymous
NM_024080.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.39
Genes affected
TRPM8 (HGNC:17961): (transient receptor potential cation channel subfamily M member 8) Predicted to enable ligand-gated calcium channel activity. Predicted to be involved in calcium ion transmembrane transport and positive regulation of cold-induced thermogenesis. Predicted to act upstream of or within several processes, including cellular calcium ion homeostasis; response to cold; and thermoception. Located in 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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 2-233942727-C-G is Benign according to our data. Variant chr2-233942727-C-G is described in ClinVar as [Benign]. Clinvar id is 769595.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=1.39 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00521 (793/152302) while in subpopulation AFR AF= 0.0177 (734/41562). AF 95% confidence interval is 0.0166. There are 10 homozygotes in gnomad4. There are 375 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRPM8 | NM_024080.5 | c.678C>G | p.Leu226= | synonymous_variant | 6/26 | ENST00000324695.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRPM8 | ENST00000324695.9 | c.678C>G | p.Leu226= | synonymous_variant | 6/26 | 1 | NM_024080.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00518 AC: 789AN: 152184Hom.: 9 Cov.: 31
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GnomAD3 exomes AF: 0.00146 AC: 368AN: 251480Hom.: 5 AF XY: 0.00113 AC XY: 153AN XY: 135916
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GnomAD4 exome AF: 0.000746 AC: 1090AN: 1461854Hom.: 11 Cov.: 31 AF XY: 0.000672 AC XY: 489AN XY: 727222
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GnomAD4 genome ? AF: 0.00521 AC: 793AN: 152302Hom.: 10 Cov.: 31 AF XY: 0.00504 AC XY: 375AN XY: 74468
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at