17-3573879-A-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_080704.4(TRPV1):c.1857T>G(p.Pro619=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000977 in 1,593,092 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (4 hom., cov: 30)
  • Exomes 𝑓: 0.00095 (32 hom.)
• Consequence: TRPV1 NM_080704.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.14

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 17-3573879-A-C is Benign according to our data. Variant chr17-3573879-A-C is described in ClinVar as [Benign]. Clinvar id is 723409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.14 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00127 (192/151578) while in subpopulation EAS AF= 0.0293 (149/5086). AF 95% confidence interval is 0.0255. There are 4 homozygotes in gnomad4. There are 117 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 192 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.1857T>G	p.Pro619=	synonymous_variant	14/17	ENST00000572705.2
TRPV1	NM_018727.5	c.1857T>G	p.Pro619=	synonymous_variant	13/16
TRPV1	NM_080705.4	c.1857T>G	p.Pro619=	synonymous_variant	13/16
TRPV1	NM_080706.3	c.1857T>G	p.Pro619=	synonymous_variant	12/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.1857T>G	p.Pro619=	synonymous_variant	14/17	1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.00127 AC: 192 AN: 151466 Hom.: 4 Cov.: 30

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0292

Gnomad SAS AF: 0.00714

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00145

GnomAD3 exomes AF: 0.00321 AC: 706 AN: 219864 Hom.: 18 AF XY: 0.00300 AC XY: 364 AN XY: 121342

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000630

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0321

Gnomad SAS exome AF: 0.00530

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000513

Gnomad OTH exome AF: 0.000917

GnomAD4 exome AF: 0.000947 AC: 1365 AN: 1441514 Hom.: 32 Cov.: 33 AF XY: 0.00106 AC XY: 762 AN XY: 716576

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000710

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0223

Gnomad4 SAS exome AF: 0.00476

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.00133

GnomAD4 genome AF: 0.00127 AC: 192 AN: 151578 Hom.: 4 Cov.: 30 AF XY: 0.00158 AC XY: 117 AN XY: 74074

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.000197

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0293

Gnomad4 SAS AF: 0.00715

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.00143

Alfa AF: 0.000189 Hom.: 0

Bravo AF: 0.00157

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.1
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs375458057; hg19: chr17-3477173;