rs222747

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-3589906-C-A
• chr17-3589906-C-G
• chr17-3589906-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080704.4(TRPV1):​c.945G>T​(p.Met315Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,446,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044552237).

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>T	p.Met315Ile	missense	Exon 7 of 17	NP_542435.2	Q8NER1-1
	TRPV1	NM_018727.5		c.945G>T	p.Met315Ile	missense	Exon 6 of 16	NP_061197.4	Q8NER1-1
	TRPV1	NM_080705.4		c.945G>T	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>T	p.Met315Ile	missense	Exon 7 of 17	ENSP00000459962.1	Q8NER1-1
	TRPV1	ENST00000425167.6	TSL:1	c.945G>T	p.Met315Ile	missense	Exon 5 of 16	ENSP00000409627.2	E7EQ78
	TRPV1	ENST00000399756.8	TSL:1	c.945G>T	p.Met315Ile	missense	Exon 5 of 15	ENSP00000382659.4	Q8NER1-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1446102 Hom.: 0 Cov.: 83 AF XY: 0.00 AC XY: 0 AN XY: 717984

African (AFR) AF: 0.00 AC: 0 AN: 33066

American (AMR) AF: 0.00 AC: 0 AN: 41752

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25776

East Asian (EAS) AF: 0.00 AC: 0 AN: 38752

South Asian (SAS) AF: 0.00 AC: 0 AN: 83816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 9.05e-7 AC: 1 AN: 1104856

Other (OTH) AF: 0.00 AC: 0 AN: 59856

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	10
DANN	Benign	0.42
DEOGEN2	Benign	0.24	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.79
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.027	T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.6	N
PhyloP100		0.81
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.068
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)
MVP		0.23
MPC		0.070
ClinPred		0.070	T
GERP RS		2.9
Varity_R		0.15
gMVP		0.29

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;