Genetic Variant NM_080704.4:c.-33-3776C>G (chr17-3596159-G-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.-33-3776C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,146 control chromosomes in the GnomAD database, including 6,280 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 0.16 ( 6280 hom., cov: 32)

Consequence

TRPV1
NM_080704.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0340

Publications

1 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:

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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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4 link	c.-33-3776C>G		intron_variant	Intron 2 of 16	ENST00000572705.2	NP_542435.2	Q8NER1-1
TRPV1	NM_018727.5 link	c.-34+759C>G		intron_variant	Intron 1 of 15		NP_061197.4	Q8NER1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRPV1	ENST00000572705.2 link	c.-33-3776C>G	intron_variant	Intron 2 of 16	1	NM_080704.4	ENSP00000459962.1	Q8NER1-1
TRPV1	ENST00000571088.5 link	c.-34+759C>G	intron_variant	Intron 1 of 15	1		ENSP00000461007.1	Q8NER1-1
ENSG00000262304	ENST00000572919.1 link	n.*1252-3776C>G	intron_variant	Intron 7 of 13	5		ENSP00000461416.1	A0A0B4J2A0

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24182

AN:

152026

Hom.:

6261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.546

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0661

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0233

Gnomad SAS

AF:

0.00643

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00268

Gnomad OTH

AF:

0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.159

AC:

24247

AN:

152146

Hom.:

6280

Cov.:

AF XY:

0.154

AC XY:

11481

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.546

AC:

22617

AN:

41440

American (AMR)

AF:

0.0660

AC:

1009

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3468

East Asian (EAS)

AF:

0.0233

AC:

121

AN:

5184

South Asian (SAS)

AF:

0.00622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00266

AC:

181

AN:

67998

Other (OTH)

AF:

0.114

AC:

241

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

570

1140

1710

2280

2850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

190

380

570

760

950

<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:

0.0231

Hom.:

Bravo

AF:

0.184

Asia WGS

AF:

0.0450

AC:

157

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.1

(source)

DANN

Benign

0.44

PhyloP100

-0.034

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over