8-72029895-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_007332.3(TRPA1):c.2937+6T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00445 in 1,613,732 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (36 hom.)
• Consequence: TRPA1 NM_007332.3 splice_donor_region, intron
• Scores: Splicing: ADA: 0.1393
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.37

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=-0.45).
• BP6: Variant 8-72029895-A-G is Benign according to our data. Variant chr8-72029895-A-G is described in ClinVar as [Benign]. Clinvar id is 788822.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 535 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRPA1	NM_007332.3	c.2937+6T>C		splice_donor_region_variant, intron_variant		ENST00000262209.5
MSC-AS1	NR_033652.1	n.1029-22644A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRPA1	ENST00000262209.5	c.2937+6T>C		splice_donor_region_variant, intron_variant		1	NM_007332.3	P1
MSC-AS1	ENST00000518916.5	n.392-22644A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00352 AC: 535 AN: 152198 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00836

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00460

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.00436 AC: 1095 AN: 251014 Hom.: 4 AF XY: 0.00456 AC XY: 618 AN XY: 135646

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00854

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00235

Gnomad FIN exome AF: 0.0140

Gnomad NFE exome AF: 0.00490

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00454 AC: 6639 AN: 1461416 Hom.: 36 Cov.: 30 AF XY: 0.00455 AC XY: 3311 AN XY: 727030

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.00163

Gnomad4 ASJ exome AF: 0.00823

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00218

Gnomad4 FIN exome AF: 0.0134

Gnomad4 NFE exome AF: 0.00459

Gnomad4 OTH exome AF: 0.00518

GnomAD4 genome AF: 0.00351 AC: 535 AN: 152316 Hom.: 2 Cov.: 32 AF XY: 0.00365 AC XY: 272 AN XY: 74484

Gnomad4 AFR AF: 0.000505

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.00836

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.00460

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00414 Hom.: 1

Bravo AF: 0.00264

EpiCase AF: 0.00360

EpiControl AF: 0.00415

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	TRPA1: BP4, BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	9.1
Dann	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.14
dbscSNV1_RF	Benign	0.28
SpliceAI score (max)		0.19		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: rs186828882; hg19: chr8-72942130;