NM_080704.4:c.285-221T>C

Variant names:

• chr17-3591574-A-G
• rs150846
• NM_080704.4:c.285-221T>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.285-221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,146 control chromosomes in the GnomAD database, including 22,311 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 0.51 (22311 hom., cov: 33)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 8 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.285-221T>C		intron_variant	Intron 3 of 16	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.285-221T>C		intron_variant	Intron 2 of 15		NP_061197.4
TRPV1	NM_080705.4	c.285-221T>C		intron_variant	Intron 2 of 15		NP_542436.2
TRPV1	NM_080706.3	c.285-221T>C		intron_variant	Intron 1 of 14		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.285-221T>C		intron_variant	Intron 3 of 16	1	NM_080704.4	ENSP00000459962.1
ENSG00000262304	ENST00000572919.1	n.*1569-221T>C		intron_variant	Intron 8 of 13	5		ENSP00000461416.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77912 AN: 152028 Hom.: 22303 Cov.: 33

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.586

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.512 AC: 77939 AN: 152146 Hom.: 22311 Cov.: 33 AF XY: 0.516 AC XY: 38422 AN XY: 74406

African (AFR) AF: 0.237 AC: 9838 AN: 41514

American (AMR) AF: 0.586 AC: 8972 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1751 AN: 3470

East Asian (EAS) AF: 0.694 AC: 3581 AN: 5158

South Asian (SAS) AF: 0.531 AC: 2560 AN: 4824

European-Finnish (FIN) AF: 0.672 AC: 7119 AN: 10594

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.621 AC: 42226 AN: 67970

Other (OTH) AF: 0.539 AC: 1138 AN: 2112

Alfa AF: 0.585 Hom.: 50219

Bravo AF: 0.497

Asia WGS AF: 0.538 AC: 1871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.33
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs150846; hg19: chr17-3494868;