Genetic Variant NM_080704.4:c.-33-4833A>G (chr17-3597216-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080704.4(TRPV1):c.-33-4833A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 155,618 control chromosomes in the GnomAD database, including 15,509 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 15395 hom., cov: 32)

Exomes 𝑓: 0.24 ( 114 hom. )

Consequence

TRPV1
NM_080704.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.16

Publications

9 publications found

Variant links:

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]

TRPV1 links:

ENSG00000262304 (HGNC:):

ENSG00000262304 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4 link	c.-33-4833A>G		intron_variant	Intron 2 of 16	ENST00000572705.2	NP_542435.2	Q8NER1-1
TRPV1	NM_018727.5 link	c.-332A>G		upstream_gene_variant			NP_061197.4	Q8NER1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPV1	ENST00000572705.2 link	c.-33-4833A>G	intron_variant	Intron 2 of 16	1	NM_080704.4	ENSP00000459962.1	Q8NER1-1
ENSG00000262304	ENST00000572919.1 link	n.*1252-4833A>G	intron_variant	Intron 7 of 13	5		ENSP00000461416.1	A0A0B4J2A0
TRPV1	ENST00000571088.5 link	c.-332A>G	upstream_gene_variant		1		ENSP00000461007.1	Q8NER1-1

Frequencies

GnomAD3 genomes

AF:

0.397

AC:

60343

AN:

151952

Hom.:

15358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.731

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.340

Gnomad ASJ

AF:

0.267

Gnomad EAS

AF:

0.187

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.222

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.377

GnomAD4 exome

AF:

0.240

AC:

850

AN:

3548

Hom.:

114

AF XY:

0.234

AC XY:

444

AN XY:

1898

show subpopulations

African (AFR)

AF:

0.707

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

AN:

East Asian (EAS)

AF:

0.195

AC:

AN:

456

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.195

AC:

AN:

370

Middle Eastern (MID)

AF:

0.333

AC:

AN:

European-Non Finnish (NFE)

AF:

0.231

AC:

533

AN:

2306

Other (OTH)

AF:

0.333

AC:

AN:

180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

121

151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.397

AC:

60431

AN:

152070

Hom.:

15395

Cov.:

AF XY:

0.390

AC XY:

29006

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.732

AC:

30328

AN:

41456

American (AMR)

AF:

0.340

AC:

5186

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

926

AN:

3472

East Asian (EAS)

AF:

0.187

AC:

968

AN:

5180

South Asian (SAS)

AF:

0.290

AC:

1399

AN:

4822

European-Finnish (FIN)

AF:

0.222

AC:

2351

AN:

10586

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.267

AC:

18174

AN:

67984

Other (OTH)

AF:

0.376

AC:

793

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1562

3123

4685

6246

7808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.303

Hom.:

33815

Bravo

AF:

0.420

Asia WGS

AF:

0.240

AC:

834

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.8

(source)

DANN

Benign

0.70

PhyloP100

-1.2

PromoterAI

0.012

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over