1-167085743-C-T

Variant names:

• chr1-167085743-C-T
• rs1041236
• NM_005814.3:c.43+4502G>A

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+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
• 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPA33	NM_005814.3	c.43+4502G>A		intron_variant	Intron 1 of 6	ENST00000367868.4	NP_005805.1
GPA33	XM_017000005.2	c.-348-3432G>A		intron_variant	Intron 1 of 7		XP_016855494.1
GPA33	XM_047424480.1	c.-456-3432G>A		intron_variant	Intron 1 of 8		XP_047280436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPA33	ENST00000367868.4	c.43+4502G>A		intron_variant	Intron 1 of 6	1	NM_005814.3	ENSP00000356842.3
GPA33	ENST00000632571.1	c.-281-12204G>A		intron_variant	Intron 1 of 3	4		ENSP00000488407.1
GPA33	ENST00000534512.1	n.44-3432G>A		intron_variant	Intron 1 of 4	4		ENSP00000431195.1

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

African (AFR) AF: 0.217 AC: 8998 AN: 41492

American (AMR) AF: 0.274 AC: 4180 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3468

East Asian (EAS) AF: 0.721 AC: 3731 AN: 5178

South Asian (SAS) AF: 0.331 AC: 1594 AN: 4812

European-Finnish (FIN) AF: 0.257 AC: 2721 AN: 10580

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19014 AN: 67980

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.286 Hom.: 16094

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
PhyloP100		1.2
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: rs1041236; hg19: chr1-167054980;