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GeneBe

2-233926549-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_024080.5(TRPM8):c.12G>A(p.Arg4=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0023 in 1,613,948 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0024 ( 5 hom. )

Consequence

TRPM8
NM_024080.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.75
Variant links:
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 -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-233926549-G-A is Benign according to our data. Variant chr2-233926549-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 723767.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=1.75 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRPM8NM_024080.5 linkuse as main transcriptc.12G>A p.Arg4= synonymous_variant 2/26 ENST00000324695.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRPM8ENST00000324695.9 linkuse as main transcriptc.12G>A p.Arg4= synonymous_variant 2/261 NM_024080.5 P1Q7Z2W7-1
TRPM8ENST00000444298.5 linkuse as main transcriptc.12G>A p.Arg4= synonymous_variant, NMD_transcript_variant 2/251
TRPM8ENST00000433712.6 linkuse as main transcriptc.-712G>A 5_prime_UTR_variant 2/245

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00166
AC:
252
AN:
152064
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000604
Gnomad AMI
AF:
0.00768
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000830
Gnomad FIN
AF:
0.000189
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00301
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00160
AC:
401
AN:
251408
Hom.:
2
AF XY:
0.00166
AC XY:
226
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.000677
Gnomad AMR exome
AF:
0.000723
Gnomad ASJ exome
AF:
0.000794
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00163
Gnomad FIN exome
AF:
0.0000924
Gnomad NFE exome
AF:
0.00253
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.00237
AC:
3464
AN:
1461766
Hom.:
5
Cov.:
30
AF XY:
0.00241
AC XY:
1755
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.000760
Gnomad4 ASJ exome
AF:
0.000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00157
Gnomad4 FIN exome
AF:
0.000356
Gnomad4 NFE exome
AF:
0.00281
Gnomad4 OTH exome
AF:
0.00190
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00166
AC:
252
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.00163
AC XY:
121
AN XY:
74396
show subpopulations
Gnomad4 AFR
AF:
0.000602
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000831
Gnomad4 FIN
AF:
0.000189
Gnomad4 NFE
AF:
0.00301
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00232
Hom.:
0
Bravo
AF:
0.00171
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.00278
EpiControl
AF:
0.00284

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 submitterclinical testingInvitaeJun 15, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
Cadd
Benign
3.4
Dann
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs149800225; hg19: chr2-234835194; COSMIC: COSV61224951; COSMIC: COSV61224951; API