ENST00000632571.1:c.-281-16984T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 20 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
LOC124904451	XR_007066717.1	n.175-263A>G		intron_variant	Intron 2 of 2
GPA33	NM_005814.3	c.-236T>C		upstream_gene_variant		ENST00000367868.4	NP_005805.1
GPA33	XM_017000005.2	c.-627T>C		upstream_gene_variant			XP_016855494.1
GPA33	XM_047424480.1	c.-735T>C		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>C		intron_variant	Intron 1 of 3	4		ENSP00000488407.1
ENSG00000299380	ENST00000763061.1	n.130+2170T>C		intron_variant	Intron 1 of 1
GPA33	ENST00000367868.4	c.-236T>C		upstream_gene_variant		1	NM_005814.3	ENSP00000356842.3
GPA33	ENST00000534512.1	n.-236T>C		upstream_gene_variant		4		ENSP00000431195.1

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

African (AFR) AF: 0.389 AC: 4752 AN: 12208

American (AMR) AF: 0.277 AC: 5153 AN: 18628

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 5446 AN: 13362

East Asian (EAS) AF: 0.186 AC: 5647 AN: 30334

South Asian (SAS) AF: 0.286 AC: 12498 AN: 43758

European-Finnish (FIN) AF: 0.486 AC: 14345 AN: 29494

Middle Eastern (MID) AF: 0.478 AC: 960 AN: 2008

European-Non Finnish (NFE) AF: 0.445 AC: 116606 AN: 262206

Other (OTH) AF: 0.405 AC: 10267 AN: 25330

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

African (AFR) AF: 0.388 AC: 16078 AN: 41404

American (AMR) AF: 0.337 AC: 5147 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3468

East Asian (EAS) AF: 0.182 AC: 941 AN: 5158

South Asian (SAS) AF: 0.250 AC: 1204 AN: 4814

European-Finnish (FIN) AF: 0.508 AC: 5355 AN: 10544

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.443 AC: 30127 AN: 67958

Other (OTH) AF: 0.426 AC: 896 AN: 2102

Alfa AF: 0.424 Hom.: 61799

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
PhyloP100		0.40
PromoterAI		0.067	Neutral
Mutation Taster		=300/0	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: rs2281962; hg19: chr1-167059760;