chr17-3573879-A-C

Variant names:

• chr17-3573879-A-C
• rs375458057
• NM_080704.4:c.1857T>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_080704.4(TRPV1):​c.1857T>G​(p.Pro619Pro) 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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High AC in GnomAd4 at 192 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	NM_080704.4	MANE Select	c.1857T>G	p.Pro619Pro	synonymous	Exon 14 of 17	NP_542435.2	Q8NER1-1
	TRPV1	NM_018727.5		c.1857T>G	p.Pro619Pro	synonymous	Exon 13 of 16	NP_061197.4	Q8NER1-1
	TRPV1	NM_080705.4		c.1857T>G	p.Pro619Pro	synonymous	Exon 13 of 16	NP_542436.2	Q8NER1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPV1	ENST00000572705.2	TSL:1 MANE Select	c.1857T>G	p.Pro619Pro	synonymous	Exon 14 of 17	ENSP00000459962.1	Q8NER1-1
	TRPV1	ENST00000425167.6	TSL:1	c.1890T>G	p.Pro630Pro	synonymous	Exon 13 of 16	ENSP00000409627.2	E7EQ78
	TRPV1	ENST00000399756.8	TSL:1	c.1857T>G	p.Pro619Pro	synonymous	Exon 12 of 15	ENSP00000382659.4	Q8NER1-1

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

GnomAD2 exomes AF: 0.00321 AC: 706 AN: 219864 AF XY: 0.00300

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 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

African (AFR) AF: 0.00 AC: 0 AN: 32980

American (AMR) AF: 0.0000710 AC: 3 AN: 42236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25318

East Asian (EAS) AF: 0.0223 AC: 858 AN: 38496

South Asian (SAS) AF: 0.00476 AC: 402 AN: 84422

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49102

Middle Eastern (MID) AF: 0.000754 AC: 4 AN: 5302

European-Non Finnish (NFE) AF: 0.0000172 AC: 19 AN: 1104362

Other (OTH) AF: 0.00133 AC: 79 AN: 59296

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

African (AFR) AF: 0.0000483 AC: 2 AN: 41394

American (AMR) AF: 0.000197 AC: 3 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.0293 AC: 149 AN: 5086

South Asian (SAS) AF: 0.00715 AC: 34 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67784

Other (OTH) AF: 0.00143 AC: 3 AN: 2098

Alfa AF: 0.000189 Hom.: 0

Bravo AF: 0.00157

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.71
PhyloP100		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs375458057; hg19: chr17-3477173;