9-133256205-G-C

Variant names:

• chr9-133256205-G-C
• rs7853989
• ENST00000611156.4:c.523C>G

Variant summary

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

The ENST00000611156.4(ABO):​c.523C>G​(p.Arg175Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,612,732 control chromosomes in the GnomAD database, including 12,420 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 0.13 (1551 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10869 hom.)
• Consequence: ABO ENST00000611156.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390
• Publications: 107 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=0.005328357).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 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.537C>G		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.523C>G	p.Arg175Gly	missense	Exon 8 of 8	ENSP00000483265.1
	ABO	ENST00000453660.4	TSL:1	n.555C>G		non_coding_transcript_exon	Exon 7 of 7
	ABO	ENST00000538324.2	TSL:5	c.523C>G	p.Arg175Gly	missense	Exon 8 of 9	ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19843 AN: 152054 Hom.: 1549 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0914

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.120

GnomAD2 exomes AF: 0.132 AC: 32364 AN: 244556 AF XY: 0.140

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.0663

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.182

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.0987

Gnomad OTH exome AF: 0.123

GnomAD4 exome AF: 0.109 AC: 159318 AN: 1460558 Hom.: 10869 Cov.: 81 AF XY: 0.114 AC XY: 83059 AN XY: 726598

African (AFR) AF: 0.169 AC: 5646 AN: 33454

American (AMR) AF: 0.0677 AC: 3020 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 3400 AN: 26088

East Asian (EAS) AF: 0.181 AC: 7186 AN: 39668

South Asian (SAS) AF: 0.268 AC: 23095 AN: 86204

European-Finnish (FIN) AF: 0.155 AC: 8199 AN: 52934

Middle Eastern (MID) AF: 0.159 AC: 914 AN: 5766

European-Non Finnish (NFE) AF: 0.0905 AC: 100576 AN: 1111506

Other (OTH) AF: 0.121 AC: 7282 AN: 60344

GnomAD4 genome AF: 0.130 AC: 19857 AN: 152174 Hom.: 1551 Cov.: 33 AF XY: 0.134 AC XY: 9975 AN XY: 74404

African (AFR) AF: 0.163 AC: 6780 AN: 41474

American (AMR) AF: 0.0915 AC: 1401 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 481 AN: 3472

East Asian (EAS) AF: 0.182 AC: 940 AN: 5174

South Asian (SAS) AF: 0.265 AC: 1281 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1623 AN: 10614

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6961 AN: 67994

Other (OTH) AF: 0.119 AC: 251 AN: 2112

Alfa AF: 0.0887 Hom.: 170

Bravo AF: 0.121

TwinsUK AF: 0.0879 AC: 326

ALSPAC AF: 0.0791 AC: 305

ESP6500AA AF: 0.155 AC: 644

ESP6500EA AF: 0.0910 AC: 765

ExAC AF: 0.134 AC: 16131

Asia WGS AF: 0.203 AC: 704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	9.7
DANN	Benign	0.46
DEOGEN2	Benign	0.063	T
FATHMM_MKL	Benign	0.072	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0053	T
PhyloP100		-0.039
PrimateAI	Benign	0.41	T
Sift4G	Benign	0.29	T
Vest4		0.048
GERP RS		-1.1
gMVP		0.64

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: rs7853989; hg19: chr9-136131592; COSMIC: COSV71743505;