17-3571516-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_080704.4(TRPV1):c.2347+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000974 in 1,583,438 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00051 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0010 (2 hom.)
• Consequence: TRPV1 NM_080704.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002389
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.281

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-3571516-C-T is Benign according to our data. Variant chr17-3571516-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 726690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 78 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.2347+8G>A		splice_region_variant, intron_variant		ENST00000572705.2
TRPV1	NM_018727.5	c.2347+8G>A		splice_region_variant, intron_variant
TRPV1	NM_080705.4	c.2347+8G>A		splice_region_variant, intron_variant
TRPV1	NM_080706.3	c.2347+8G>A		splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.2347+8G>A		splice_region_variant, intron_variant		1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.000512 AC: 78 AN: 152256 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000313

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000867

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000528 AC: 108 AN: 204442 Hom.: 0 AF XY: 0.000571 AC XY: 63 AN XY: 110266

Gnomad AFR exome AF: 0.000254

Gnomad AMR exome AF: 0.0000338

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000679

Gnomad SAS exome AF: 0.000663

Gnomad FIN exome AF: 0.000108

Gnomad NFE exome AF: 0.000915

Gnomad OTH exome AF: 0.000378

GnomAD4 exome AF: 0.00102 AC: 1464 AN: 1431064 Hom.: 2 Cov.: 30 AF XY: 0.000985 AC XY: 699 AN XY: 709320

Gnomad4 AFR exome AF: 0.000183

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000118

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000526

Gnomad4 FIN exome AF: 0.0000584

Gnomad4 NFE exome AF: 0.00126

Gnomad4 OTH exome AF: 0.000540

GnomAD4 genome AF: 0.000512 AC: 78 AN: 152374 Hom.: 0 Cov.: 33 AF XY: 0.000362 AC XY: 27 AN XY: 74512

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000867

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000736 Hom.: 0

Bravo AF: 0.000487

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.8
Dann	Benign	0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000024
dbscSNV1_RF	Benign	0.026
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

Publications

LitVar

Other links and lift over

dbSNP: rs200793682; hg19: chr17-3474810; COSMIC: COSV99440483; COSMIC: COSV99440483;