rs222738

Variant names:

• chr17-3601921-C-T
• rs222738
• NM_080704.4:c.-34+6506G>A

Variant summary

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

The NM_080704.4(TRPV1):​c.-34+6506G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 152,194 control chromosomes in the GnomAD database, including 739 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 0.088 (739 hom., cov: 30)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: TRPV1 NM_080704.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.212 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	NM_080704.4	MANE Select	c.-34+6506G>A		intron	N/A	NP_542435.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	ENST00000572705.2	TSL:1 MANE Select	c.-34+6506G>A		intron	N/A	ENSP00000459962.1
	ENSG00000262304	ENST00000572919.1	TSL:5	n.*1251+7388G>A		intron	N/A	ENSP00000461416.1
	ENSG00000261916	ENST00000575593.1	TSL:6	n.352G>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0876 AC: 13327 AN: 152062 Hom.: 734 Cov.: 30

Gnomad AFR AF: 0.0330

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0879

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.0875

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.0847

GnomAD4 exome AF: 0.0714 AC: 1 AN: 14 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 1 AN: 12

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0877 AC: 13350 AN: 152180 Hom.: 739 Cov.: 30 AF XY: 0.0909 AC XY: 6760 AN XY: 74400

African (AFR) AF: 0.0330 AC: 1371 AN: 41536

American (AMR) AF: 0.101 AC: 1549 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0879 AC: 305 AN: 3468

East Asian (EAS) AF: 0.222 AC: 1149 AN: 5168

South Asian (SAS) AF: 0.216 AC: 1041 AN: 4828

European-Finnish (FIN) AF: 0.0875 AC: 927 AN: 10590

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0986 AC: 6707 AN: 67998

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.0977 Hom.: 576

Bravo AF: 0.0840

Asia WGS AF: 0.282 AC: 983 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	0.41
DANN	Benign	0.75
PhyloP100		-1.1

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: rs222738; hg19: chr17-3505215;