rs12040913

Variant names:

• chr1-167088399-G-A
• rs12040913
• NM_005814.3:c.43+1846C>T

Variant summary

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

The NM_005814.3(GPA33):​c.43+1846C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,828 control chromosomes in the GnomAD database, including 12,951 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 (12951 hom., cov: 32)
• Consequence: GPA33 NM_005814.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.385
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005814.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPA33	NM_005814.3	MANE Select	c.43+1846C>T		intron	N/A	NP_005805.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPA33	ENST00000367868.4	TSL:1 MANE Select	c.43+1846C>T		intron	N/A	ENSP00000356842.3
	GPA33	ENST00000632571.1	TSL:4	c.-281-14860C>T		intron	N/A	ENSP00000488407.1
	GPA33	ENST00000534512.1	TSL:4	n.43+1846C>T		intron	N/A	ENSP00000431195.1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61866 AN: 151710 Hom.: 12942 Cov.: 32

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.408 AC: 61918 AN: 151828 Hom.: 12951 Cov.: 32 AF XY: 0.404 AC XY: 29931 AN XY: 74170

African (AFR) AF: 0.406 AC: 16828 AN: 41400

American (AMR) AF: 0.337 AC: 5146 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1390 AN: 3460

East Asian (EAS) AF: 0.179 AC: 922 AN: 5164

South Asian (SAS) AF: 0.250 AC: 1206 AN: 4822

European-Finnish (FIN) AF: 0.481 AC: 5050 AN: 10502

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29974 AN: 67894

Other (OTH) AF: 0.423 AC: 894 AN: 2112

Alfa AF: 0.434 Hom.: 1882

Bravo AF: 0.396

Asia WGS AF: 0.220 AC: 766 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.33
PhyloP100		0.39
Mutation Taster		=100/0	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: rs12040913; hg19: chr1-167057636;