rs7527143

Positions:

• chr1-167158117-G-A
• chr1-167158117-G-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000632571.1(GPA33):​c.-282+8166C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 151,000 control chromosomes in the GnomAD database, including 21,459 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 0.53 (21459 hom., cov: 31)
• Consequence: GPA33 ENST00000632571.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPA33	ENST00000632571.1	c.-282+8166C>T		intron_variant		4		ENSP00000488407

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80051 AN: 150884 Hom.: 21426 Cov.: 31

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.531 AC: 80125 AN: 151000 Hom.: 21459 Cov.: 31 AF XY: 0.533 AC XY: 39339 AN XY: 73752

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.553

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.654

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.552

Alfa AF: 0.516 Hom.: 9666

Bravo AF: 0.536

Asia WGS AF: 0.661 AC: 2298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	12
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7527143; hg19: chr1-167127354;