rs612169

Positions:

• chr9-133268030-G-A

Variant summary

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

The NM_020469.3(ABO):​c.29-5862C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,858 control chromosomes in the GnomAD database, including 29,151 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 (29151 hom., cov: 32)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

ABO (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABO	NM_020469.3	c.29-5862C>T		intron_variant			NP_065202.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000538324.2	c.29-5862C>T		intron_variant		5		ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93544 AN: 151742 Hom.: 29129 Cov.: 32

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.616 AC: 93607 AN: 151858 Hom.: 29151 Cov.: 32 AF XY: 0.615 AC XY: 45600 AN XY: 74192

Gnomad4 AFR AF: 0.549

Gnomad4 AMR AF: 0.716

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.634

Alfa AF: 0.640 Hom.: 30119

Bravo AF: 0.630

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs612169; hg19: chr9-136143442;