Genetic Variant NM_080704.4:c.*708T>C (chr17-3566107-A-G) – 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.*708T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 151,800 control chromosomes in the GnomAD database, including 67,158 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 0.94 ( 67106 hom., cov: 27)

Exomes 𝑓: 0.99 ( 52 hom. )

Consequence

TRPV1
NM_080704.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

4 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:

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=-1.01).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
TRPV1	NM_080704.4 link	c.*708T>C	3_prime_UTR_variant	Exon 17 of 17	ENST00000572705.2	NP_542435.2	Q8NER1-1
TRPV1	NM_018727.5 link	c.*708T>C	3_prime_UTR_variant	Exon 16 of 16		NP_061197.4	Q8NER1-1
TRPV1	NM_080705.4 link	c.*708T>C	3_prime_UTR_variant	Exon 16 of 16		NP_542436.2	Q8NER1-1
TRPV1	NM_080706.3 link	c.*708T>C	3_prime_UTR_variant	Exon 15 of 15		NP_542437.2	Q8NER1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRPV1	ENST00000572705.2 link	c.*708T>C		3_prime_UTR_variant	Exon 17 of 17	1	NM_080704.4	ENSP00000459962.1		Q8NER1-1

Frequencies

GnomAD3 genomes

AF:

0.940

AC:

142447

AN:

151576

Hom.:

67052

Cov.:

show subpopulations

Gnomad AFR

AF:

0.883

Gnomad AMI

AF:

0.964

Gnomad AMR

AF:

0.972

Gnomad ASJ

AF:

0.949

Gnomad EAS

AF:

0.966

Gnomad SAS

AF:

0.954

Gnomad FIN

AF:

0.985

Gnomad MID

AF:

0.962

Gnomad NFE

AF:

0.955

Gnomad OTH

AF:

0.962

GnomAD4 exome

AF:

0.991

AC:

105

AN:

106

Hom.:

Cov.:

AF XY:

1.00

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.988

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.940

AC:

142559

AN:

151694

Hom.:

67106

Cov.:

AF XY:

0.942

AC XY:

69785

AN XY:

74090

show subpopulations

African (AFR)

AF:

0.884

AC:

36496

AN:

41308

American (AMR)

AF:

0.972

AC:

14803

AN:

15230

Ashkenazi Jewish (ASJ)

AF:

0.949

AC:

3292

AN:

3468

East Asian (EAS)

AF:

0.966

AC:

4976

AN:

5150

South Asian (SAS)

AF:

0.954

AC:

4568

AN:

4790

European-Finnish (FIN)

AF:

0.985

AC:

10361

AN:

10520

Middle Eastern (MID)

AF:

0.963

AC:

283

AN:

294

European-Non Finnish (NFE)

AF:

0.955

AC:

64879

AN:

67920

Other (OTH)

AF:

0.962

AC:

2026

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

408

815

1223

1630

2038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.946

Hom.:

8463

Bravo

AF:

0.937

Asia WGS

AF:

0.961

AC:

3343

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

0.62

(source)

DANN

Benign

0.45

PhyloP100

-1.1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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