chr9-133255669-CG-C

Variant names:

• chr9-133255669-CG-C
• rs56392308
• ENST00000611156.4:c.1058delC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000611156.4(ABO):​c.1058delC​(p.Pro353ArgfsTer23) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.064 in 1,597,388 control chromosomes in the GnomAD database, including 3,759 homozygotes. Variant has been reported in ClinVar as Affects (no stars).

• Frequency:
  • Genomes: 𝑓 0.063 (367 hom., cov: 31)
  • Exomes 𝑓: 0.064 (3392 hom.)
• Consequence: ABO ENST00000611156.4 frameshift
• Clinical Significance: Affects no assertion criteria provided O:1
• Conservation: PhyloP100: -1.10
• Publications: 49 publications found

Genes affected

ABO (HGNC:79): (ABO, alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase) This gene encodes proteins related to the first discovered blood group system, ABO. Variation in the ABO gene (chromosome 9q34.2) is the basis of the ABO blood group, thus the presence of an allele determines the blood group in an individual. The 'O' blood group is caused by a deletion of guanine-258 near the N-terminus of the protein which results in a frameshift and translation of an almost entirely different protein. Individuals with the A, B, and AB alleles express glycosyltransferase activities that convert the H antigen into the A or B antigen. Other minor alleles have been found for this gene. [provided by RefSeq, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000611156.4. 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
	ABO	NR_198898.1		n.1072delC		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.1058delC	p.Pro353ArgfsTer23	frameshift	Exon 8 of 8	ENSP00000483265.1
	ABO	ENST00000453660.4	TSL:1	n.1090delC		non_coding_transcript_exon	Exon 7 of 7
	ABO	ENST00000538324.2	TSL:5	c.1054delC	p.Arg352ValfsTer22	frameshift splice_region	Exon 9 of 9	ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9545 AN: 151988 Hom.: 367 Cov.: 31

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0664

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0589

GnomAD2 exomes AF: 0.0561 AC: 11836 AN: 210860 AF XY: 0.0564

Gnomad AFR exome AF: 0.0647

Gnomad AMR exome AF: 0.0275

Gnomad ASJ exome AF: 0.0758

Gnomad EAS exome AF: 0.000129

Gnomad FIN exome AF: 0.106

Gnomad NFE exome AF: 0.0692

Gnomad OTH exome AF: 0.0601

GnomAD4 exome AF: 0.0641 AC: 92652 AN: 1445282 Hom.: 3392 Cov.: 41 AF XY: 0.0628 AC XY: 45095 AN XY: 717730

African (AFR) AF: 0.0575 AC: 1901 AN: 33088

American (AMR) AF: 0.0295 AC: 1224 AN: 41514

Ashkenazi Jewish (ASJ) AF: 0.0702 AC: 1809 AN: 25778

East Asian (EAS) AF: 0.0000515 AC: 2 AN: 38810

South Asian (SAS) AF: 0.0304 AC: 2567 AN: 84436

European-Finnish (FIN) AF: 0.103 AC: 5286 AN: 51140

Middle Eastern (MID) AF: 0.0655 AC: 376 AN: 5738

European-Non Finnish (NFE) AF: 0.0688 AC: 75995 AN: 1104978

Other (OTH) AF: 0.0584 AC: 3492 AN: 59800

GnomAD4 genome AF: 0.0628 AC: 9551 AN: 152106 Hom.: 367 Cov.: 31 AF XY: 0.0637 AC XY: 4739 AN XY: 74344

African (AFR) AF: 0.0603 AC: 2499 AN: 41446

American (AMR) AF: 0.0423 AC: 647 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 230 AN: 3466

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5164

South Asian (SAS) AF: 0.0292 AC: 141 AN: 4826

European-Finnish (FIN) AF: 0.115 AC: 1222 AN: 10602

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4564 AN: 67988

Other (OTH) AF: 0.0582 AC: 123 AN: 2112

Alfa AF: 0.0617 Hom.: 56

Bravo AF: 0.0574

Asia WGS AF: 0.0200 AC: 69 AN: 3478

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

ABO blood group system Other:1

Aug 31, 1992

OMIM

Significance: Affects

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56392308; hg19: chr9-136131056; COSMIC: COSV71743673;