17-3573900-C-T

Position:

• chr17-3573900-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The ENST00000572705.2(TRPV1):​c.1836G>A​(p.Thr612=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,610,324 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (28 hom., cov: 30)
  • Exomes 𝑓: 0.0014 (30 hom.)
• Consequence: TRPV1 ENST00000572705.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-3573900-C-T is Benign according to our data. Variant chr17-3573900-C-T is described in ClinVar as [Benign]. Clinvar id is 778654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.42 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1743/151932) while in subpopulation AFR AF= 0.0396 (1641/41420). AF 95% confidence interval is 0.038. There are 28 homozygotes in gnomad4. There are 816 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1743 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRPV1	NM_080704.4	c.1836G>A	p.Thr612=	synonymous_variant	14/17	ENST00000572705.2	NP_542435.2
TRPV1	NM_018727.5	c.1836G>A	p.Thr612=	synonymous_variant	13/16		NP_061197.4
TRPV1	NM_080705.4	c.1836G>A	p.Thr612=	synonymous_variant	13/16		NP_542436.2
TRPV1	NM_080706.3	c.1836G>A	p.Thr612=	synonymous_variant	12/15		NP_542437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2	c.1836G>A	p.Thr612=	synonymous_variant	14/17	1	NM_080704.4	ENSP00000459962	P1

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1732 AN: 151814 Hom.: 28 Cov.: 30

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00375

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000624

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000353

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00315 AC: 770 AN: 244388 Hom.: 10 AF XY: 0.00251 AC XY: 334 AN XY: 133046

Gnomad AFR exome AF: 0.0415

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000565

Gnomad SAS exome AF: 0.00163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000226

Gnomad OTH exome AF: 0.00169

GnomAD4 exome AF: 0.00142 AC: 2075 AN: 1458392 Hom.: 30 Cov.: 33 AF XY: 0.00137 AC XY: 994 AN XY: 725600

Gnomad4 AFR exome AF: 0.0451

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00164

Gnomad4 FIN exome AF: 0.0000376

Gnomad4 NFE exome AF: 0.000141

Gnomad4 OTH exome AF: 0.00309

GnomAD4 genome AF: 0.0115 AC: 1743 AN: 151932 Hom.: 28 Cov.: 30 AF XY: 0.0110 AC XY: 816 AN XY: 74254

Gnomad4 AFR AF: 0.0396

Gnomad4 AMR AF: 0.00374

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00713 Hom.: 5

Bravo AF: 0.0135

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.54
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Publications

LitVar

Other links and lift over

dbSNP: rs114179863; hg19: chr17-3477194;