rs2277675

Variant names:

• chr17-3597216-T-C
• rs2277675
• NM_080704.4:c.-33-4833A>G

Variant summary

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

The NM_080704.4(TRPV1):​c.-33-4833A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 155,618 control chromosomes in the GnomAD database, including 15,509 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 0.40 (15395 hom., cov: 32)
  • Exomes 𝑓: 0.24 (114 hom.)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 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.-33-4833A>G		intron	N/A	NP_542435.2	Q8NER1-1
	TRPV1	NM_018727.5		c.-332A>G		upstream_gene	N/A	NP_061197.4	Q8NER1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	ENST00000572705.2	TSL:1 MANE Select	c.-33-4833A>G		intron	N/A	ENSP00000459962.1	Q8NER1-1
	ENSG00000262304	ENST00000572919.1	TSL:5	n.*1252-4833A>G		intron	N/A	ENSP00000461416.1
	TRPV1	ENST00000571088.5	TSL:1	c.-332A>G		upstream_gene	N/A	ENSP00000461007.1	Q8NER1-1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60343 AN: 151952 Hom.: 15358 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.240 AC: 850 AN: 3548 Hom.: 114 AF XY: 0.234 AC XY: 444 AN XY: 1898

African (AFR) AF: 0.707 AC: 41 AN: 58

American (AMR) AF: 0.500 AC: 23 AN: 46

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 20 AN: 96

East Asian (EAS) AF: 0.195 AC: 89 AN: 456

South Asian (SAS) AF: 0.333 AC: 8 AN: 24

European-Finnish (FIN) AF: 0.195 AC: 72 AN: 370

Middle Eastern (MID) AF: 0.333 AC: 4 AN: 12

European-Non Finnish (NFE) AF: 0.231 AC: 533 AN: 2306

Other (OTH) AF: 0.333 AC: 60 AN: 180

GnomAD4 genome AF: 0.397 AC: 60431 AN: 152070 Hom.: 15395 Cov.: 32 AF XY: 0.390 AC XY: 29006 AN XY: 74344

African (AFR) AF: 0.732 AC: 30328 AN: 41456

American (AMR) AF: 0.340 AC: 5186 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3472

East Asian (EAS) AF: 0.187 AC: 968 AN: 5180

South Asian (SAS) AF: 0.290 AC: 1399 AN: 4822

European-Finnish (FIN) AF: 0.222 AC: 2351 AN: 10586

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18174 AN: 67984

Other (OTH) AF: 0.376 AC: 793 AN: 2108

Alfa AF: 0.303 Hom.: 33815

Bravo AF: 0.420

Asia WGS AF: 0.240 AC: 834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.70
PhyloP100		-1.2
PromoterAI		0.012	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2277675;

hg19: chr17-3500510;