Genetic Variant TRPM8:c.2761+259T>C (chr2-233983483-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_024080.5(TRPM8):c.2761+259T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 456,912 control chromosomes in the GnomAD database, including 139,365 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 0.78 ( 47014 hom., cov: 33)

Exomes 𝑓: 0.77 ( 92351 hom. )

Consequence

TRPM8
NM_024080.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.72

Publications

5 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:

Genome browser will be placed here

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=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.824 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.2761+259T>C	intron	N/A	NP_076985.4
TRPM8	NM_001397606.1		c.2761+259T>C	intron	N/A	NP_001384535.1
TRPM8	NM_001397607.1		c.2611+259T>C	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.2761+259T>C	intron	N/A	ENSP00000323926.4	Q7Z2W7-1
TRPM8	ENST00000439148.1	TSL:1	n.407+132T>C	intron	N/A	ENSP00000390609.1	H7BZP4
TRPM8	ENST00000444298.5	TSL:1	n.*1710+259T>C	intron	N/A	ENSP00000396745.1	F8WD55

Frequencies

GnomAD3 genomes

AF:

0.783

AC:

119006

AN:

152068

Hom.:

46974

Cov.:

show subpopulations

Gnomad AFR

AF:

0.753

Gnomad AMI

AF:

0.887

Gnomad AMR

AF:

0.743

Gnomad ASJ

AF:

0.826

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.539

Gnomad FIN

AF:

0.841

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.830

Gnomad OTH

AF:

0.788

GnomAD4 exome

AF:

0.770

AC:

234519

AN:

304726

Hom.:

92351

AF XY:

0.751

AC XY:

121457

AN XY:

161738

show subpopulations

African (AFR)

AF:

0.763

AC:

6476

AN:

8488

American (AMR)

AF:

0.718

AC:

9959

AN:

13878

Ashkenazi Jewish (ASJ)

AF:

0.832

AC:

6966

AN:

8372

East Asian (EAS)

AF:

0.589

AC:

9415

AN:

15992

South Asian (SAS)

AF:

0.547

AC:

23472

AN:

42872

European-Finnish (FIN)

AF:

0.832

AC:

23311

AN:

28010

Middle Eastern (MID)

AF:

0.828

AC:

1118

AN:

1350

European-Non Finnish (NFE)

AF:

0.832

AC:

141049

AN:

169600

Other (OTH)

AF:

0.789

AC:

12753

AN:

16164

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

2474

4948

7421

9895

12369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

604

1208

1812

2416

3020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.783

AC:

119102

AN:

152186

Hom.:

47014

Cov.:

AF XY:

0.775

AC XY:

57686

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.754

AC:

31280

AN:

41506

American (AMR)

AF:

0.742

AC:

11343

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.826

AC:

2868

AN:

3472

East Asian (EAS)

AF:

0.573

AC:

2972

AN:

5184

South Asian (SAS)

AF:

0.540

AC:

2601

AN:

4820

European-Finnish (FIN)

AF:

0.841

AC:

8910

AN:

10596

Middle Eastern (MID)

AF:

0.837

AC:

246

AN:

294

European-Non Finnish (NFE)

AF:

0.830

AC:

56418

AN:

68008

Other (OTH)

AF:

0.784

AC:

1655

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1330

2660

3991

5321

6651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

858

1716

2574

3432

4290

<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:

0.811

Hom.:

154745

Bravo

AF:

0.781

Asia WGS

AF:

0.552

AC:

1920

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.078

(source)

DANN

Benign

0.36

PhyloP100

-3.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over