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GeneBe

rs35427625

chr8-72050874-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007332.3(TRPA1):c.1812-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 1,589,380 control chromosomes in the GnomAD database, including 8,124 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 963 hom., cov: 33)
Exomes 𝑓: 0.095 ( 7161 hom. )

Consequence

TRPA1
NM_007332.3 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.001182
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.87
Variant links:
Genes affected
TRPA1 (HGNC:497): (transient receptor potential cation channel subfamily A member 1) The structure of the protein encoded by this gene is highly related to both the protein ankyrin and transmembrane proteins. The specific function of this protein has not yet been determined; however, studies indicate the function may involve a role in signal transduction and growth control. [provided by RefSeq, Jul 2008]
MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-72050874-G-A is Benign according to our data. Variant chr8-72050874-G-A is described in ClinVar as [Benign]. Clinvar id is 3055480.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRPA1NM_007332.3 linkuse as main transcriptc.1812-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000262209.5
MSC-AS1NR_033652.1 linkuse as main transcriptn.1029-1665G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRPA1ENST00000262209.5 linkuse as main transcriptc.1812-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_007332.3 P1
MSC-AS1ENST00000518916.5 linkuse as main transcriptn.392-1665G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.104
AC:
15788
AN:
152026
Hom.:
966
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.139
Gnomad AMI
AF:
0.0515
Gnomad AMR
AF:
0.101
Gnomad ASJ
AF:
0.118
Gnomad EAS
AF:
0.00154
Gnomad SAS
AF:
0.102
Gnomad FIN
AF:
0.0471
Gnomad MID
AF:
0.130
Gnomad NFE
AF:
0.0993
Gnomad OTH
AF:
0.113
GnomAD3 exomes
AF:
0.0870
AC:
21560
AN:
247828
Hom.:
1145
AF XY:
0.0898
AC XY:
12060
AN XY:
134254
show subpopulations
Gnomad AFR exome
AF:
0.138
Gnomad AMR exome
AF:
0.0671
Gnomad ASJ exome
AF:
0.117
Gnomad EAS exome
AF:
0.000436
Gnomad SAS exome
AF:
0.113
Gnomad FIN exome
AF:
0.0444
Gnomad NFE exome
AF:
0.0969
Gnomad OTH exome
AF:
0.0999
GnomAD4 exome
AF:
0.0945
AC:
135857
AN:
1437236
Hom.:
7161
Cov.:
27
AF XY:
0.0957
AC XY:
68568
AN XY:
716706
show subpopulations
Gnomad4 AFR exome
AF:
0.140
Gnomad4 AMR exome
AF:
0.0707
Gnomad4 ASJ exome
AF:
0.115
Gnomad4 EAS exome
AF:
0.000354
Gnomad4 SAS exome
AF:
0.112
Gnomad4 FIN exome
AF:
0.0453
Gnomad4 NFE exome
AF:
0.0978
Gnomad4 OTH exome
AF:
0.0947
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.104
AC:
15796
AN:
152144
Hom.:
963
Cov.:
33
AF XY:
0.101
AC XY:
7542
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.139
Gnomad4 AMR
AF:
0.100
Gnomad4 ASJ
AF:
0.118
Gnomad4 EAS
AF:
0.00154
Gnomad4 SAS
AF:
0.103
Gnomad4 FIN
AF:
0.0471
Gnomad4 NFE
AF:
0.0993
Gnomad4 OTH
AF:
0.112
Alfa
AF:
0.0978
Hom.:
304
Bravo
AF:
0.107
Asia WGS
AF:
0.0560
AC:
195
AN:
3478
EpiCase
AF:
0.102
EpiControl
AF:
0.106

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

TRPA1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 28, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
12
Dann
Benign
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0012
dbscSNV1_RF
Benign
0.13
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.23
Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35427625; hg19: chr8-72963109; API