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GeneBe

rs28546865

chr8-72069083-G-Achr8-72069083-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_007332.3(TRPA1):c.384C>T(p.Asn128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,613,846 control chromosomes in the GnomAD database, including 15,076 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2452 hom., cov: 32)
Exomes 𝑓: 0.12 ( 12624 hom. )

Consequence

TRPA1
NM_007332.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28
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 -15 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=-0.61).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 8-72069083-G-A is Benign according to our data. Variant chr8-72069083-G-A is described in ClinVar as [Benign]. Clinvar id is 3058871.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.28 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TRPA1NM_007332.3 linkuse as main transcriptc.384C>T p.Asn128= synonymous_variant 3/27 ENST00000262209.5
TRPA1XM_011517624.3 linkuse as main transcriptc.459C>T p.Asn153= synonymous_variant 4/28
TRPA1XM_011517625.3 linkuse as main transcriptc.384C>T p.Asn128= synonymous_variant 5/29

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRPA1ENST00000262209.5 linkuse as main transcriptc.384C>T p.Asn128= synonymous_variant 3/271 NM_007332.3 P1
MSC-AS1ENST00000518916.5 linkuse as main transcriptn.470-7438G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.161
AC:
24537
AN:
152028
Hom.:
2445
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.276
Gnomad AMI
AF:
0.0822
Gnomad AMR
AF:
0.0893
Gnomad ASJ
AF:
0.141
Gnomad EAS
AF:
0.287
Gnomad SAS
AF:
0.180
Gnomad FIN
AF:
0.109
Gnomad MID
AF:
0.108
Gnomad NFE
AF:
0.108
Gnomad OTH
AF:
0.156
GnomAD3 exomes
AF:
0.138
AC:
34765
AN:
251478
Hom.:
3065
AF XY:
0.139
AC XY:
18884
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.281
Gnomad AMR exome
AF:
0.0693
Gnomad ASJ exome
AF:
0.134
Gnomad EAS exome
AF:
0.305
Gnomad SAS exome
AF:
0.180
Gnomad FIN exome
AF:
0.114
Gnomad NFE exome
AF:
0.107
Gnomad OTH exome
AF:
0.111
GnomAD4 exome
AF:
0.123
AC:
179123
AN:
1461700
Hom.:
12624
Cov.:
37
AF XY:
0.124
AC XY:
90052
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.278
Gnomad4 AMR exome
AF:
0.0706
Gnomad4 ASJ exome
AF:
0.136
Gnomad4 EAS exome
AF:
0.312
Gnomad4 SAS exome
AF:
0.181
Gnomad4 FIN exome
AF:
0.112
Gnomad4 NFE exome
AF:
0.108
Gnomad4 OTH exome
AF:
0.130
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.161
AC:
24558
AN:
152146
Hom.:
2452
Cov.:
32
AF XY:
0.161
AC XY:
11938
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.276
Gnomad4 AMR
AF:
0.0891
Gnomad4 ASJ
AF:
0.141
Gnomad4 EAS
AF:
0.286
Gnomad4 SAS
AF:
0.179
Gnomad4 FIN
AF:
0.109
Gnomad4 NFE
AF:
0.108
Gnomad4 OTH
AF:
0.157
Alfa
AF:
0.130
Hom.:
768
Bravo
AF:
0.163
Asia WGS
AF:
0.192
AC:
668
AN:
3478
EpiCase
AF:
0.103
EpiControl
AF:
0.108

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 SciencesNov 19, 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
-0.61
Cadd
Benign
5.6
Dann
Benign
0.66

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

LitVar

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

Other links and lift over

dbSNP: rs28546865; hg19: chr8-72981318; COSMIC: COSV51569245; COSMIC: COSV51569245; API