rs8176719

Variant names:

• chr9-133257521-T-TC
• rs8176719
• ENST00000611156.4:c.259-1_259insG

Variant summary

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

The ENST00000611156.4(ABO):​c.259-1_259insG variant causes a splice acceptor, splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.358 in 1,612,876 control chromosomes in the GnomAD database, including 106,427 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (10022 hom., cov: 0)
  • Exomes 𝑓: 0.36 (96405 hom.)
• Consequence: ABO ENST00000611156.4 splice_acceptor, splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 293 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 (SAS) allele frequency at 95% confidence interval = 0.431 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	NR_198898.1		n.272_273insG		non_coding_transcript_exon	Exon 6 of 7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.259-1_259insG		splice_acceptor splice_donor intron	N/A	ENSP00000483265.1	A0A087X0C2
	ABO	ENST00000453660.4	TSL:1	n.290_291insG		non_coding_transcript_exon	Exon 6 of 7
	ABO	ENST00000538324.2	TSL:5	c.259-1_259insG		splice_acceptor splice_donor intron	N/A	ENSP00000483018.1	A0A087X009

Frequencies

GnomAD3 genomes AF: 0.354 AC: 53648 AN: 151592 Hom.: 10015 Cov.: 0

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.384

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.350

GnomAD2 exomes AF: 0.368 AC: 91421 AN: 248556 AF XY: 0.379

Gnomad AFR exome AF: 0.310

Gnomad AMR exome AF: 0.216

Gnomad ASJ exome AF: 0.430

Gnomad EAS exome AF: 0.375

Gnomad FIN exome AF: 0.470

Gnomad NFE exome AF: 0.373

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.358 AC: 523814 AN: 1461166 Hom.: 96405 Cov.: 37 AF XY: 0.364 AC XY: 264432 AN XY: 726878

African (AFR) AF: 0.302 AC: 10120 AN: 33466

American (AMR) AF: 0.223 AC: 9958 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 10924 AN: 26128

East Asian (EAS) AF: 0.428 AC: 16989 AN: 39676

South Asian (SAS) AF: 0.456 AC: 39286 AN: 86230

European-Finnish (FIN) AF: 0.463 AC: 24720 AN: 53368

Middle Eastern (MID) AF: 0.389 AC: 2235 AN: 5752

European-Non Finnish (NFE) AF: 0.350 AC: 388564 AN: 1111508

Other (OTH) AF: 0.348 AC: 21018 AN: 60348

GnomAD4 genome AF: 0.354 AC: 53677 AN: 151710 Hom.: 10022 Cov.: 0 AF XY: 0.357 AC XY: 26462 AN XY: 74116

African (AFR) AF: 0.304 AC: 12524 AN: 41264

American (AMR) AF: 0.283 AC: 4323 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1468 AN: 3468

East Asian (EAS) AF: 0.384 AC: 1970 AN: 5134

South Asian (SAS) AF: 0.447 AC: 2147 AN: 4806

European-Finnish (FIN) AF: 0.477 AC: 5023 AN: 10540

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24770 AN: 67920

Other (OTH) AF: 0.348 AC: 732 AN: 2106

Alfa AF: 0.363 Hom.: 2033

Bravo AF: 0.333

Asia WGS AF: 0.395 AC: 1372 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs8176719; hg19: chr9-136132908; COSMIC: COSV107533852;