rs1041236

chr1-167085743-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005814.3(GPA33):c.43+4502G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,108 control chromosomes in the GnomAD database, including 6,655 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 0.28 (6655 hom., cov: 33)
• Consequence: GPA33 NM_005814.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPA33	NM_005814.3	c.43+4502G>A		intron_variant		ENST00000367868.4
GPA33	XM_017000005.2	c.-348-3432G>A		intron_variant
GPA33	XM_047424480.1	c.-456-3432G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPA33	ENST00000367868.4	c.43+4502G>A		intron_variant		1	NM_005814.3	P1
GPA33	ENST00000632571.1	c.-281-12204G>A		intron_variant		4
GPA33	ENST00000534512.1	c.44-3432G>A		intron_variant, NMD_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42521 AN: 151990 Hom.: 6658 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.297

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

GnomAD4 genome AF: 0.280 AC: 42531 AN: 152108 Hom.: 6655 Cov.: 33 AF XY: 0.283 AC XY: 21024 AN XY: 74348

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.368

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.294

Alfa AF: 0.289 Hom.: 11199

Bravo AF: 0.283

Asia WGS AF: 0.501 AC: 1746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	9.9
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs1041236; hg19: chr1-167054980;