rs73028893

Positions:

• chr1-167077218-A-G

Variant summary

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

The NM_005814.3(GPA33):​c.44-3679T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0801 in 151,958 control chromosomes in the GnomAD database, including 1,170 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 0.080 (1170 hom., cov: 31)
• Consequence: GPA33 NM_005814.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPA33	NM_005814.3	c.44-3679T>C		intron_variant		ENST00000367868.4	NP_005805.1
GPA33	XM_017000005.2	c.-281-3679T>C		intron_variant			XP_016855494.1
GPA33	XM_047424480.1	c.-281-3679T>C		intron_variant			XP_047280436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPA33	ENST00000367868.4	c.44-3679T>C		intron_variant		1	NM_005814.3	ENSP00000356842	P1
GPA33	ENST00000632571.1	c.-281-3679T>C		intron_variant		4		ENSP00000488407
GPA33	ENST00000534512.1	c.111-3679T>C		intron_variant, NMD_transcript_variant		4		ENSP00000431195
GPA33	ENST00000527955.5	n.134+1368T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0801 AC: 12160 AN: 151840 Hom.: 1171 Cov.: 31

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.0131

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0222

Gnomad OTH AF: 0.0661

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

GnomAD4 genome AF: 0.0801 AC: 12167 AN: 151958 Hom.: 1170 Cov.: 31 AF XY: 0.0766 AC XY: 5693 AN XY: 74282

Gnomad4 AFR AF: 0.231

Gnomad4 AMR AF: 0.0467

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00560

Gnomad4 FIN AF: 0.0131

Gnomad4 NFE AF: 0.0222

Gnomad4 OTH AF: 0.0654

Alfa AF: 0.0567 Hom.: 94

Bravo AF: 0.0912

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.71

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: rs73028893; hg19: chr1-167046455;