rs2281962

Positions:

• chr1-167090523-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000632571.1(GPA33):​c.-281-16984T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 589,254 control chromosomes in the GnomAD database, including 50,056 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 0.41 (12906 hom., cov: 31)
  • Exomes 𝑓: 0.40 (37150 hom.)
• Consequence: GPA33 ENST00000632571.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395

Genes affected

GPA33 (HGNC:4445): (glycoprotein A33) The glycoprotein encoded by this gene is a cell surface antigen that is expressed in greater than 95% of human colon cancers. The open reading frame encodes a 319-amino acid polypeptide having a putative secretory signal sequence and 3 potential glycosylation sites. The predicted mature protein has a 213-amino acid extracellular region, a single transmembrane domain, and a 62-amino acid intracellular tail. The sequence of the extracellular region contains 2 domains characteristic of the CD2 subgroup of the immunoglobulin (Ig) superfamily. [provided by RefSeq, Jul 2008]

LOC124904451 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124904451	XR_007066717.1	n.175-263A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPA33	ENST00000632571.1	c.-281-16984T>C		intron_variant		4		ENSP00000488407.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61635 AN: 151808 Hom.: 12901 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.402 AC: 175674 AN: 437328 Hom.: 37150 Cov.: 0 AF XY: 0.397 AC XY: 91608 AN XY: 230768

Gnomad4 AFR exome AF: 0.389

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.186

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.486

Gnomad4 NFE exome AF: 0.445

Gnomad4 OTH exome AF: 0.405

GnomAD4 genome AF: 0.406 AC: 61665 AN: 151926 Hom.: 12906 Cov.: 31 AF XY: 0.403 AC XY: 29894 AN XY: 74248

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.443

Gnomad4 OTH AF: 0.426

Alfa AF: 0.429 Hom.: 29716

Bravo AF: 0.391

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.5
DANN	Benign	0.58

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

Other links and lift over

dbSNP: rs2281962; hg19: chr1-167059760;