chr9-133257647-G-T

Variant names:

• chr9-133257647-G-T
• rs8176717
• ENST00000611156.4:c.240-105C>A

Variant summary

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

The ENST00000611156.4(ABO):​c.240-105C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,391,948 control chromosomes in the GnomAD database, including 42,320 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 0.26 (5392 hom., cov: 32)
  • Exomes 𝑓: 0.24 (36928 hom.)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 18 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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.373 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.252-105C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.240-105C>A		intron	N/A	ENSP00000483265.1
	ABO	ENST00000453660.4	TSL:1	n.270-105C>A		intron	N/A
	ABO	ENST00000538324.2	TSL:5	c.240-105C>A		intron	N/A	ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39149 AN: 151800 Hom.: 5387 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.248

GnomAD4 exome AF: 0.239 AC: 296211 AN: 1240030 Hom.: 36928 AF XY: 0.236 AC XY: 144663 AN XY: 612464

African (AFR) AF: 0.261 AC: 7405 AN: 28350

American (AMR) AF: 0.454 AC: 14798 AN: 32614

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 5883 AN: 21640

East Asian (EAS) AF: 0.258 AC: 8977 AN: 34760

South Asian (SAS) AF: 0.199 AC: 13900 AN: 69866

European-Finnish (FIN) AF: 0.174 AC: 6337 AN: 36392

Middle Eastern (MID) AF: 0.218 AC: 799 AN: 3668

European-Non Finnish (NFE) AF: 0.234 AC: 225048 AN: 960454

Other (OTH) AF: 0.250 AC: 13064 AN: 52286

GnomAD4 genome AF: 0.258 AC: 39169 AN: 151918 Hom.: 5392 Cov.: 32 AF XY: 0.257 AC XY: 19114 AN XY: 74264

African (AFR) AF: 0.268 AC: 11087 AN: 41318

American (AMR) AF: 0.381 AC: 5820 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3468

East Asian (EAS) AF: 0.269 AC: 1385 AN: 5156

South Asian (SAS) AF: 0.213 AC: 1025 AN: 4816

European-Finnish (FIN) AF: 0.178 AC: 1890 AN: 10590

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16319 AN: 67978

Other (OTH) AF: 0.246 AC: 519 AN: 2110

Alfa AF: 0.260 Hom.: 8533

Bravo AF: 0.278

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.62
PhyloP100		-1.2
RBP_binding_hub_radar		1.0
RBP_regulation_power_radar		3.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs8176717; hg19: chr9-136133034; COSMIC: COSV71743436;