rs4656525

Positions:

• chr1-167152428-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

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 = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPA33	ENST00000632571.1	c.-282+13855C>T		intron_variant		4

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

Gnomad4 AFR AF: 0.0285

Gnomad4 AMR AF: 0.0970

Gnomad4 ASJ AF: 0.0713

Gnomad4 EAS AF: 0.00386

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.101

Alfa AF: 0.124 Hom.: 1610

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4656525; hg19: chr1-167121665;