rs12040913

Positions:

• chr1-167088399-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPA33	NM_005814.3	c.43+1846C>T		intron_variant		ENST00000367868.4	NP_005805.1
GPA33	XM_017000005.2	c.-349+1846C>T		intron_variant			XP_016855494.1
GPA33	XM_047424480.1	c.-457+1846C>T		intron_variant			XP_047280436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPA33	ENST00000367868.4	c.43+1846C>T		intron_variant		1	NM_005814.3	ENSP00000356842	P1
GPA33	ENST00000632571.1	c.-281-14860C>T		intron_variant		4		ENSP00000488407
GPA33	ENST00000534512.1	c.43+1846C>T		intron_variant, NMD_transcript_variant		4		ENSP00000431195

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

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.423

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.3
DANN	Benign	0.33

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: rs12040913; hg19: chr1-167057636;