17-3573863-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.1873G>A(p.Asp625Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000689 in 1,539,542 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000069 (1 hom.)
• Consequence: TRPV1 NM_080704.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.397

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 (MetaRNN=0.01313138).
• BP6: Variant 17-3573863-C-T is Benign according to our data. Variant chr17-3573863-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 728409.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPV1	NM_080704.4	c.1873G>A	p.Asp625Asn	missense_variant	14/17	ENST00000572705.2
TRPV1	NM_018727.5	c.1873G>A	p.Asp625Asn	missense_variant	13/16
TRPV1	NM_080705.4	c.1873G>A	p.Asp625Asn	missense_variant	13/16
TRPV1	NM_080706.3	c.1873G>A	p.Asp625Asn	missense_variant	12/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPV1	ENST00000572705.2	c.1873G>A	p.Asp625Asn	missense_variant	14/17	1	NM_080704.4	P1

Frequencies

GnomAD3 genomes AF: 0.0000665 AC: 10 AN: 150474 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000531

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000327 AC: 79 AN: 241940 Hom.: 0 AF XY: 0.000212 AC XY: 28 AN XY: 131966

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00216

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000561

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000369

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000691 AC: 96 AN: 1389068 Hom.: 1 Cov.: 34 AF XY: 0.0000563 AC XY: 39 AN XY: 692406

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00191

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000122

Gnomad4 OTH exome AF: 0.0000182

GnomAD4 genome AF: 0.0000665 AC: 10 AN: 150474 Hom.: 0 Cov.: 30 AF XY: 0.0000544 AC XY: 4 AN XY: 73476

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000531

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000120 Hom.: 0

Bravo AF: 0.000174

ExAC AF: 0.000248 AC: 30

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 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	9.2
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;D;D;D;.;.;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.035	N
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.013	T;T;T;T;T;T;T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	-0.14	N;N;N;N;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.59	N;.;.;N;N;.;N
REVEL	Benign	0.25
Sift	Benign	0.23	T;.;.;T;T;.;T
Sift4G	Benign	0.12	T;T;T;T;T;T;T
Polyphen		0.0070	B;B;B;B;B;.;B
Vest4		0.14
MVP		0.37
MPC		0.063
ClinPred		0.021	T
GERP RS		-0.66
Varity_R		0.063
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs868605933; hg19: chr17-3477157; COSMIC: COSV51525054; COSMIC: COSV51525054;