rs224534

Variant names:

• chr17-3583408-G-A
• rs224534
• NM_080704.4:c.1406C>T
• TRPV1 p.Thr469Ile

Your query was ambiguous. Multiple possible variants found:

• chr17-3583408-G-A
• chr17-3583408-G-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.1406C>T​(p.Thr469Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 1,603,258 control chromosomes in the GnomAD database, including 112,346 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 0.31 (9156 hom., cov: 33)
  • Exomes 𝑓: 0.37 (103190 hom.)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 62 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=2.0098341E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 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.1406C>T	p.Thr469Ile	missense	Exon 10 of 17	NP_542435.2	Q8NER1-1
	TRPV1	NM_018727.5		c.1406C>T	p.Thr469Ile	missense	Exon 9 of 16	NP_061197.4	Q8NER1-1
	TRPV1	NM_080705.4		c.1406C>T	p.Thr469Ile	missense	Exon 9 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.1406C>T	p.Thr469Ile	missense	Exon 10 of 17	ENSP00000459962.1	Q8NER1-1
	TRPV1	ENST00000425167.6	TSL:1	c.1439C>T	p.Thr480Ile	missense	Exon 9 of 16	ENSP00000409627.2	E7EQ78
	TRPV1	ENST00000399756.8	TSL:1	c.1406C>T	p.Thr469Ile	missense	Exon 8 of 15	ENSP00000382659.4	Q8NER1-1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46534 AN: 152086 Hom.: 9151 Cov.: 33

Gnomad AFR AF: 0.0805

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.464

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.318

GnomAD2 exomes AF: 0.394 AC: 92858 AN: 235758 AF XY: 0.395

Gnomad AFR exome AF: 0.0709

Gnomad AMR exome AF: 0.399

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.771

Gnomad FIN exome AF: 0.454

Gnomad NFE exome AF: 0.357

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.366 AC: 530538 AN: 1451054 Hom.: 103190 Cov.: 34 AF XY: 0.368 AC XY: 265019 AN XY: 720904

African (AFR) AF: 0.0662 AC: 2211 AN: 33374

American (AMR) AF: 0.392 AC: 16950 AN: 43280

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 9972 AN: 25826

East Asian (EAS) AF: 0.753 AC: 29739 AN: 39488

South Asian (SAS) AF: 0.418 AC: 35271 AN: 84362

European-Finnish (FIN) AF: 0.450 AC: 23820 AN: 52912

Middle Eastern (MID) AF: 0.347 AC: 1998 AN: 5752

European-Non Finnish (NFE) AF: 0.351 AC: 388657 AN: 1106022

Other (OTH) AF: 0.365 AC: 21920 AN: 60038

GnomAD4 genome AF: 0.306 AC: 46546 AN: 152204 Hom.: 9156 Cov.: 33 AF XY: 0.316 AC XY: 23543 AN XY: 74412

African (AFR) AF: 0.0804 AC: 3340 AN: 41568

American (AMR) AF: 0.369 AC: 5636 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1331 AN: 3470

East Asian (EAS) AF: 0.771 AC: 3990 AN: 5178

South Asian (SAS) AF: 0.433 AC: 2090 AN: 4828

European-Finnish (FIN) AF: 0.464 AC: 4907 AN: 10578

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24232 AN: 67986

Other (OTH) AF: 0.325 AC: 686 AN: 2112

Alfa AF: 0.342 Hom.: 38263

Bravo AF: 0.291

Asia WGS AF: 0.608 AC: 2114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.89	D
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0000020	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		1.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.012	D
Varity_R		0.094
gMVP		0.23
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.010		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.

Other links and lift over

dbSNP: rs224534;

hg19: chr17-3486702;

COSMIC: COSV51516848;

COSMIC: COSV51516848;