8-72029975-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007332.3(TRPA1):c.2869-6C>A 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 0.607 in 1,610,630 control chromosomes in the GnomAD database, including 299,729 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (30320 hom., cov: 32)
  • Exomes 𝑓: 0.61 (269409 hom.)
• Consequence: TRPA1 NM_007332.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.001980
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.483

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)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-72029975-G-T is Benign according to our data. Variant chr8-72029975-G-T is described in ClinVar as [Benign]. Clinvar id is 1342279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPA1	NM_007332.3	c.2869-6C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000262209.5
MSC-AS1	NR_033652.1	n.1029-22564G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.2869-6C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.392-22564G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95450 AN: 151900 Hom.: 30277 Cov.: 32

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.649

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.682

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.638

GnomAD3 exomes AF: 0.643 AC: 161375 AN: 250870 Hom.: 52791 AF XY: 0.637 AC XY: 86312 AN XY: 135576

Gnomad AFR exome AF: 0.651

Gnomad AMR exome AF: 0.806

Gnomad ASJ exome AF: 0.657

Gnomad EAS exome AF: 0.686

Gnomad SAS exome AF: 0.669

Gnomad FIN exome AF: 0.559

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.634

GnomAD4 exome AF: 0.605 AC: 882891 AN: 1458610 Hom.: 269409 Cov.: 38 AF XY: 0.606 AC XY: 439736 AN XY: 725742

Gnomad4 AFR exome AF: 0.659

Gnomad4 AMR exome AF: 0.798

Gnomad4 ASJ exome AF: 0.656

Gnomad4 EAS exome AF: 0.671

Gnomad4 SAS exome AF: 0.667

Gnomad4 FIN exome AF: 0.567

Gnomad4 NFE exome AF: 0.588

Gnomad4 OTH exome AF: 0.620

GnomAD4 genome AF: 0.628 AC: 95541 AN: 152020 Hom.: 30320 Cov.: 32 AF XY: 0.631 AC XY: 46870 AN XY: 74298

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.649

Gnomad4 EAS AF: 0.693

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.636

Alfa AF: 0.583 Hom.: 7131

Bravo AF: 0.643

Asia WGS AF: 0.696 AC: 2422 AN: 3476

EpiCase AF: 0.588

EpiControl AF: 0.587

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial episodic pain syndrome with predominantly upper body involvement Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.23
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0020
dbscSNV1_RF	Benign	0.26
SpliceAI score (max)		0.050		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

Other links and lift over

dbSNP: rs3824151; hg19: chr8-72942210; COSMIC: COSV51557555; COSMIC: COSV51557555;