9-133256028-C-T

Variant names:

• chr9-133256028-C-T
• rs8176743
• ENST00000611156.4:c.700G>A

Variant summary

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

The ENST00000611156.4(ABO):​c.700G>A​(p.Gly234Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 1,584,348 control chromosomes in the GnomAD database, including 9,335 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as no classification for the single variant (no stars).

• Frequency:
  • Genomes: 𝑓 0.12 (1298 hom., cov: 32)
  • Exomes 𝑓: 0.089 (8037 hom.)
• Consequence: ABO ENST00000611156.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.461
• Publications: 123 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 (MetaRNN=0.0038890243).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 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.714G>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.700G>A	p.Gly234Ser	missense	Exon 8 of 8	ENSP00000483265.1
	ABO	ENST00000453660.4	TSL:1	n.732G>A		non_coding_transcript_exon	Exon 7 of 7
	ABO	ENST00000538324.2	TSL:5	c.700G>A	p.Gly234Ser	missense	Exon 8 of 9	ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17487 AN: 151862 Hom.: 1296 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0540

Gnomad AMR AF: 0.0742

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.119 AC: 23681 AN: 199484 AF XY: 0.127

Gnomad AFR exome AF: 0.168

Gnomad AMR exome AF: 0.0567

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.183

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.0765

Gnomad OTH exome AF: 0.106

GnomAD4 exome AF: 0.0888 AC: 127257 AN: 1432368 Hom.: 8037 Cov.: 79 AF XY: 0.0945 AC XY: 67092 AN XY: 710326

African (AFR) AF: 0.165 AC: 5386 AN: 32636

American (AMR) AF: 0.0565 AC: 2223 AN: 39322

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 3174 AN: 25550

East Asian (EAS) AF: 0.180 AC: 6809 AN: 37738

South Asian (SAS) AF: 0.259 AC: 21420 AN: 82714

European-Finnish (FIN) AF: 0.135 AC: 6928 AN: 51146

Middle Eastern (MID) AF: 0.149 AC: 855 AN: 5732

European-Non Finnish (NFE) AF: 0.0677 AC: 74397 AN: 1098290

Other (OTH) AF: 0.102 AC: 6065 AN: 59240

GnomAD4 genome AF: 0.115 AC: 17501 AN: 151980 Hom.: 1298 Cov.: 32 AF XY: 0.119 AC XY: 8864 AN XY: 74306

African (AFR) AF: 0.159 AC: 6571 AN: 41366

American (AMR) AF: 0.0743 AC: 1136 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3470

East Asian (EAS) AF: 0.182 AC: 935 AN: 5142

South Asian (SAS) AF: 0.258 AC: 1243 AN: 4826

European-Finnish (FIN) AF: 0.137 AC: 1450 AN: 10610

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0796 AC: 5407 AN: 67960

Other (OTH) AF: 0.105 AC: 221 AN: 2114

Alfa AF: 0.0888 Hom.: 1251

Bravo AF: 0.106

TwinsUK AF: 0.0639 AC: 237

ALSPAC AF: 0.0586 AC: 226

ESP6500AA AF: 0.157 AC: 647

ESP6500EA AF: 0.0722 AC: 603

ExAC AF: 0.103 AC: 12294

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	7.6
DANN	Benign	0.62
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.14	T
MetaRNN	Benign	0.0039	T
PhyloP100		0.46
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.24	T
Vest4		0.046
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs8176743; hg19: chr9-136131415; COSMIC: COSV71743503;