rs4656525

Variant names:

• chr1-167152428-G-A
• rs4656525
• ENST00000632571.1:c.-282+13855C>T

Variant summary

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

The ENST00000632571.1(GPA33):​c.-282+13855C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 152,234 control chromosomes in the GnomAD database, including 808 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 0.091 (808 hom., cov: 32)
• Consequence: GPA33 ENST00000632571.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 1 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]

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 = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPA33	ENST00000632571.1	c.-282+13855C>T		intron_variant	Intron 1 of 3	4		ENSP00000488407.1

Frequencies

GnomAD3 genomes AF: 0.0906 AC: 13782 AN: 152116 Hom.: 810 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.0713

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0905 AC: 13778 AN: 152234 Hom.: 808 Cov.: 32 AF XY: 0.0894 AC XY: 6654 AN XY: 74426

African (AFR) AF: 0.0285 AC: 1183 AN: 41566

American (AMR) AF: 0.0970 AC: 1483 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0713 AC: 247 AN: 3466

East Asian (EAS) AF: 0.00386 AC: 20 AN: 5184

South Asian (SAS) AF: 0.128 AC: 618 AN: 4820

European-Finnish (FIN) AF: 0.103 AC: 1088 AN: 10590

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8845 AN: 67994

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.120 Hom.: 1982

Bravo AF: 0.0855

Asia WGS AF: 0.0830 AC: 290 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	6.0
DANN	Benign	0.58
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs4656525; hg19: chr1-167121665;