Genetic Variant NM_024080.5:c.2939+384G>A (chr2-233986249-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024080.5(TRPM8):c.2939+384G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,098 control chromosomes in the GnomAD database, including 2,034 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2034 hom., cov: 33)

Consequence

TRPM8
NM_024080.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.809

Publications

3 publications found

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]

TRPM8 links:

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new If you want to explore the variant's impact on the transcript NM_024080.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024080.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPM8	NM_024080.5	MANE Select	c.2939+384G>A	intron	N/A	NP_076985.4
TRPM8	NM_001397606.1		c.2939+384G>A	intron	N/A	NP_001384535.1
TRPM8	NM_001397607.1		c.2789+384G>A	intron	N/A	NP_001384536.1	A0A1L1Z857

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TRPM8	ENST00000324695.9	TSL:1 MANE Select	c.2939+384G>A	intron	N/A	ENSP00000323926.4	Q7Z2W7-1
TRPM8	ENST00000439148.1	TSL:1	n.*165+384G>A	intron	N/A	ENSP00000390609.1	H7BZP4
TRPM8	ENST00000444298.5	TSL:1	n.*1888+384G>A	intron	N/A	ENSP00000396745.1	F8WD55

Frequencies

GnomAD3 genomes

AF:

0.155

AC:

23561

AN:

151980

Hom.:

2029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.150

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.131

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.157

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.155

AC:

23570

AN:

152098

Hom.:

2034

Cov.:

AF XY:

0.159

AC XY:

11855

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.129

AC:

5367

AN:

41496

American (AMR)

AF:

0.150

AC:

2289

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

607

AN:

3472

East Asian (EAS)

AF:

0.416

AC:

2150

AN:

5164

South Asian (SAS)

AF:

0.168

AC:

809

AN:

4814

European-Finnish (FIN)

AF:

0.201

AC:

2119

AN:

10544

Middle Eastern (MID)

AF:

0.120

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.144

AC:

9819

AN:

68004

Other (OTH)

AF:

0.156

AC:

329

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1023

2046

3068

4091

5114

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.151

Hom.:

3524

Bravo

AF:

0.153

Asia WGS

AF:

0.245

AC:

850

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.3

(source)

DANN

Benign

0.81

PhyloP100

0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over