NM_080704.4:c.945G>C

Variant names:

• chr17-3589906-C-G
• rs222747
• NM_080704.4:c.945G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080704.4(TRPV1):​c.945G>C​(p.Met315Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 1,598,084 control chromosomes in the GnomAD database, including 452,995 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (45571 hom., cov: 32)
  • Exomes 𝑓: 0.75 (407424 hom.)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.807
• Publications: 90 publications found

Genes affected

TRPV1 (HGNC:12716): (transient receptor potential cation channel subfamily V member 1) Capsaicin, the main pungent ingredient in hot chili peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. The protein encoded by this gene is a receptor for capsaicin and is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. This receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo. Four transcript variants encoding the same protein, but with different 5' UTR sequence, have been described for this gene. [provided by RefSeq, Jul 2008]

ENSG00000262304 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=6.156609E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080704.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	NM_080704.4	MANE Select	c.945G>C	p.Met315Ile	missense	Exon 7 of 17	NP_542435.2	Q8NER1-1
	TRPV1	NM_018727.5		c.945G>C	p.Met315Ile	missense	Exon 6 of 16	NP_061197.4	Q8NER1-1
	TRPV1	NM_080705.4		c.945G>C	p.Met315Ile	missense	Exon 6 of 16	NP_542436.2	Q8NER1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	ENST00000572705.2	TSL:1 MANE Select	c.945G>C	p.Met315Ile	missense	Exon 7 of 17	ENSP00000459962.1	Q8NER1-1
	TRPV1	ENST00000425167.6	TSL:1	c.945G>C	p.Met315Ile	missense	Exon 5 of 16	ENSP00000409627.2	E7EQ78
	TRPV1	ENST00000399756.8	TSL:1	c.945G>C	p.Met315Ile	missense	Exon 5 of 15	ENSP00000382659.4	Q8NER1-1

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116758 AN: 152004 Hom.: 45546 Cov.: 32

Gnomad AFR AF: 0.879

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.738

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.752

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.767

GnomAD2 exomes AF: 0.723 AC: 159239 AN: 220190 AF XY: 0.725

Gnomad AFR exome AF: 0.880

Gnomad AMR exome AF: 0.733

Gnomad ASJ exome AF: 0.735

Gnomad EAS exome AF: 0.427

Gnomad FIN exome AF: 0.659

Gnomad NFE exome AF: 0.748

Gnomad OTH exome AF: 0.732

GnomAD4 exome AF: 0.748 AC: 1081985 AN: 1445960 Hom.: 407424 Cov.: 83 AF XY: 0.748 AC XY: 536803 AN XY: 717920

African (AFR) AF: 0.890 AC: 29417 AN: 33064

American (AMR) AF: 0.737 AC: 30757 AN: 41736

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 18931 AN: 25776

East Asian (EAS) AF: 0.480 AC: 18599 AN: 38742

South Asian (SAS) AF: 0.760 AC: 63655 AN: 83810

European-Finnish (FIN) AF: 0.661 AC: 34702 AN: 52462

Middle Eastern (MID) AF: 0.767 AC: 4414 AN: 5756

European-Non Finnish (NFE) AF: 0.758 AC: 836998 AN: 1104768

Other (OTH) AF: 0.744 AC: 44512 AN: 59846

GnomAD4 genome AF: 0.768 AC: 116832 AN: 152124 Hom.: 45571 Cov.: 32 AF XY: 0.760 AC XY: 56497 AN XY: 74350

African (AFR) AF: 0.879 AC: 36480 AN: 41522

American (AMR) AF: 0.740 AC: 11297 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.738 AC: 2561 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2230 AN: 5144

South Asian (SAS) AF: 0.754 AC: 3632 AN: 4816

European-Finnish (FIN) AF: 0.645 AC: 6823 AN: 10578

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51208 AN: 68002

Other (OTH) AF: 0.763 AC: 1612 AN: 2114

Alfa AF: 0.746 Hom.: 32124

Bravo AF: 0.775

TwinsUK AF: 0.751 AC: 2783

ALSPAC AF: 0.758 AC: 2923

ESP6500AA AF: 0.884 AC: 3764

ESP6500EA AF: 0.762 AC: 6471

ExAC AF: 0.712 AC: 85744

Asia WGS AF: 0.631 AC: 2197 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.58
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.027	T
MetaRNN	Benign	6.2e-7	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.81
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.066
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.41		Gain of catalytic residue at M315 (P = 0.0678)
MPC		0.070
ClinPred		0.0015	T
GERP RS		2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.29
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs222747; hg19: chr17-3493200; COSMIC: COSV51514986;