8-72053738-G-A

Variant names:

• chr8-72053738-G-A
• rs3735942
• ENST00000457356.9:n.1710G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000457356.9(MSC-AS1):​n.1710G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,586,502 control chromosomes in the GnomAD database, including 102,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10927 hom., cov: 32)
  • Exomes 𝑓: 0.35 (91851 hom.)
• Consequence: MSC-AS1 ENST00000457356.9 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.554
• Publications: 17 publications found

Genes affected

MSC-AS1 (HGNC:48724): (MSC antisense RNA 1)

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]

TRPA1 Gene-Disease associations (from GenCC):

• familial episodic pain syndrome with predominantly upper body involvement

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• hereditary peripheral neuropathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 8-72053738-G-A is Benign according to our data. Variant chr8-72053738-G-A is described in ClinVar as Benign. ClinVar VariationId is 1342281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457356.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRPA1	NM_007332.3	MANE Select	c.1644+15C>T		intron	N/A	NP_015628.2
	MSC-AS1	NR_033651.1		n.1633G>A		non_coding_transcript_exon	Exon 3 of 3
	MSC-AS1	NR_033652.1		n.2228G>A		non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSC-AS1	ENST00000457356.9	TSL:1	n.1710G>A		non_coding_transcript_exon	Exon 3 of 3
	TRPA1	ENST00000262209.5	TSL:1 MANE Select	c.1644+15C>T		intron	N/A	ENSP00000262209.4
	MSC-AS1	ENST00000519751.6	TSL:4	n.1727G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56278 AN: 151962 Hom.: 10903 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.351

GnomAD2 exomes AF: 0.398 AC: 98558 AN: 247362 AF XY: 0.383

Gnomad AFR exome AF: 0.360

Gnomad AMR exome AF: 0.638

Gnomad ASJ exome AF: 0.272

Gnomad EAS exome AF: 0.553

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.332

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.350 AC: 502436 AN: 1434422 Hom.: 91851 Cov.: 25 AF XY: 0.347 AC XY: 248008 AN XY: 714740

African (AFR) AF: 0.366 AC: 12030 AN: 32890

American (AMR) AF: 0.622 AC: 27529 AN: 44272

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 7088 AN: 25948

East Asian (EAS) AF: 0.546 AC: 21591 AN: 39510

South Asian (SAS) AF: 0.342 AC: 29128 AN: 85170

European-Finnish (FIN) AF: 0.415 AC: 22064 AN: 53194

Middle Eastern (MID) AF: 0.264 AC: 1203 AN: 4550

European-Non Finnish (NFE) AF: 0.331 AC: 360927 AN: 1089462

Other (OTH) AF: 0.351 AC: 20876 AN: 59426

GnomAD4 genome AF: 0.370 AC: 56344 AN: 152080 Hom.: 10927 Cov.: 32 AF XY: 0.376 AC XY: 27963 AN XY: 74320

African (AFR) AF: 0.366 AC: 15193 AN: 41494

American (AMR) AF: 0.505 AC: 7707 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 947 AN: 3470

East Asian (EAS) AF: 0.548 AC: 2833 AN: 5170

South Asian (SAS) AF: 0.355 AC: 1712 AN: 4818

European-Finnish (FIN) AF: 0.414 AC: 4386 AN: 10582

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.329 AC: 22378 AN: 67972

Other (OTH) AF: 0.348 AC: 736 AN: 2112

Alfa AF: 0.343 Hom.: 26939

Bravo AF: 0.382

Asia WGS AF: 0.465 AC: 1616 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.4
DANN	Benign	0.72
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3735942; hg19: chr8-72965973; COSMIC: COSV51570899; COSMIC: COSV51570899;