8-72078803-G-A

Variant names:

• chr8-72078803-G-A
• rs2587562
• ENST00000518916.5:n.576+2176G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000518916.5(MSC-AS1):​n.576+2176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,758 control chromosomes in the GnomAD database, including 15,240 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (15240 hom., cov: 32)
• Consequence: MSC-AS1 ENST00000518916.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000518916.5. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MSC-AS1	ENST00000518916.5	TSL:3	n.576+2176G>A		intron	N/A
	MSC-AS1	ENST00000767649.1		n.431+2176G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67333 AN: 151640 Hom.: 15224 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.561

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.462

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.444 AC: 67377 AN: 151758 Hom.: 15240 Cov.: 32 AF XY: 0.444 AC XY: 32928 AN XY: 74158

African (AFR) AF: 0.458 AC: 18996 AN: 41448

American (AMR) AF: 0.343 AC: 5241 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 1947 AN: 3468

East Asian (EAS) AF: 0.347 AC: 1791 AN: 5164

South Asian (SAS) AF: 0.428 AC: 2061 AN: 4812

European-Finnish (FIN) AF: 0.502 AC: 5289 AN: 10526

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30506 AN: 67760

Other (OTH) AF: 0.463 AC: 975 AN: 2104

Alfa AF: 0.446 Hom.: 56853

Bravo AF: 0.432

Asia WGS AF: 0.371 AC: 1287 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.45
DANN	Benign	0.44
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs2587562; hg19: chr8-72991038;