rs624601

chr9-133259961-G-Achr9-133259961-G-C

Variant summary

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

The NM_020469.3(ABO):c.156-95C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,126,384 control chromosomes in the GnomAD database, including 41,750 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 0.28 (6267 hom., cov: 33)
  • Exomes 𝑓: 0.26 (35483 hom.)
• Consequence: ABO NM_020469.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.156-95C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.156-95C>T		intron_variant		5		A2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42365 AN: 152042 Hom.: 6255 Cov.: 33

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.260 AC: 253783 AN: 974224 Hom.: 35483 AF XY: 0.255 AC XY: 128138 AN XY: 503456

Gnomad4 AFR exome AF: 0.348

Gnomad4 AMR exome AF: 0.484

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.270

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.279 AC: 42409 AN: 152160 Hom.: 6267 Cov.: 33 AF XY: 0.277 AC XY: 20627 AN XY: 74378

Gnomad4 AFR AF: 0.339

Gnomad4 AMR AF: 0.389

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.262

Alfa AF: 0.268 Hom.: 845

Bravo AF: 0.301

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs624601; hg19: chr9-136135365;