9-133261703-A-G

Variant names:

• chr9-133261703-A-G
• rs687289
• ENST00000611156.4:c.99-329T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000611156.4(ABO):​c.99-329T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 151,952 control chromosomes in the GnomAD database, including 29,926 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 0.62 (29926 hom., cov: 31)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 132 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (Cadd=1.51).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.707 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.111-329T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.99-329T>C		intron	N/A	ENSP00000483265.1	A0A087X0C2
	ABO	ENST00000453660.4	TSL:1	n.129-329T>C		intron	N/A
	ABO	ENST00000538324.2	TSL:5	c.99-329T>C		intron	N/A	ENSP00000483018.1	A0A087X009

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94816 AN: 151834 Hom.: 29894 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.625 AC: 94896 AN: 151952 Hom.: 29926 Cov.: 31 AF XY: 0.622 AC XY: 46187 AN XY: 74270

African (AFR) AF: 0.578 AC: 23934 AN: 41420

American (AMR) AF: 0.719 AC: 10987 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1967 AN: 3472

East Asian (EAS) AF: 0.614 AC: 3150 AN: 5130

South Asian (SAS) AF: 0.560 AC: 2699 AN: 4816

European-Finnish (FIN) AF: 0.540 AC: 5709 AN: 10578

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44588 AN: 67932

Other (OTH) AF: 0.638 AC: 1347 AN: 2110

Alfa AF: 0.647 Hom.: 120593

Bravo AF: 0.639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
CADD	Benign	1.5
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs687289;