rs2281962

Variant names:

• chr1-167090523-A-C
• rs2281962
• ENST00000632571.1:c.-281-16984T>G

Your query was ambiguous. Multiple possible variants found:

• chr1-167090523-A-C
• chr1-167090523-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000632571.1(GPA33):​c.-281-16984T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 438,102 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: GPA33 ENST00000632571.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.395
• Publications: 0 publications found

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]

ENSG00000299380 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124904451	XR_007066717.1	n.175-263A>C		intron_variant	Intron 2 of 2
GPA33	NM_005814.3	c.-236T>G		upstream_gene_variant		ENST00000367868.4	NP_005805.1
GPA33	XM_017000005.2	c.-627T>G		upstream_gene_variant			XP_016855494.1
GPA33	XM_047424480.1	c.-735T>G		upstream_gene_variant			XP_047280436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPA33	ENST00000632571.1	c.-281-16984T>G		intron_variant	Intron 1 of 3	4		ENSP00000488407.1
ENSG00000299380	ENST00000763061.1	n.130+2170T>G		intron_variant	Intron 1 of 1
GPA33	ENST00000367868.4	c.-236T>G		upstream_gene_variant		1	NM_005814.3	ENSP00000356842.3
GPA33	ENST00000534512.1	n.-236T>G		upstream_gene_variant		4		ENSP00000431195.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000228 AC: 1 AN: 438102 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 231198

African (AFR) AF: 0.00 AC: 0 AN: 12232

American (AMR) AF: 0.00 AC: 0 AN: 18654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13384

East Asian (EAS) AF: 0.00 AC: 0 AN: 30388

South Asian (SAS) AF: 0.00 AC: 0 AN: 43810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2012

European-Non Finnish (NFE) AF: 0.00000381 AC: 1 AN: 262688

Other (OTH) AF: 0.00 AC: 0 AN: 25386

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.8
DANN	Benign	0.58
PhyloP100		0.40
PromoterAI		0.015	Neutral

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: rs2281962; hg19: chr1-167059760;