ENST00000611156.4:c.29-1694T>G

Variant names:

• chr9-133263862-A-C
• rs657152
• ENST00000611156.4:c.29-1694T>G

GermlineCancer (beta)

Variant summary

Our verdict is Benign.

<-10 Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The ENST00000611156.4(ABO):c.29-1694T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000611156.4 is not a MANE Select or MANE Plus Clinical transcript for ABO; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.606 (AC=92,180) in the gnomAD database across 152,100 control chromosomes, including 28,191 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.686. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (28191 hom., cov: 33)
• Consequence: ABO ENST00000611156.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 272 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]

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Benign. The variant received -12 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
	BA1Stand-alone benign allele frequency (>5%)		GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6863 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000611156.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABO NR_198898.1		n.41-1694T>G	intron	Intron 1 of 6	Prot:

ABO NR_198898.1

HGVSc / HGVSpn.41-1694T>G

Exon rankIntron 1 of 6

intron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ABO ENST00000611156.4	TSL:5	c.29-1694T>G	intron	Intron 1 of 7	Prot: ENSP00000483265.1 UniProt:
	ABO ENST00000453660.4	TSL:1	n.59-1694T>G	intron	Intron 1 of 6	Prot:
	ABO ENST00000538324.2	TSL:5	c.29-1694T>G	intron	Intron 1 of 8	Prot: ENSP00000483018.1 UniProt:

ABO ENST00000611156.4

TSL:5

HGVSc / HGVSpc.29-1694T>G

Exon rankIntron 1 of 7

intron

Prot: ENSP00000483265.1UniProt: A0A087X0C2

ABO ENST00000453660.4

TSL:1

HGVSc / HGVSpn.59-1694T>G

Exon rankIntron 1 of 6

intron

Prot:

ABO ENST00000538324.2

TSL:5

HGVSc / HGVSpc.29-1694T>G

Exon rankIntron 1 of 8

intron

Prot: ENSP00000483018.1UniProt: A0A087X009

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.606	AC:92111	Hom:28165	AN:151982	Cov:33
GnomAD4 genome	AF: 0.606	AC:92180	Hom:28191	AN:152100	Cov:33
TOPMed (Bravo)	AF: 0.621	AC:164318	Hom:51563	AN:264690	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.624	AC:398852	Hom:125771	AN:638864	Cov:
Local & regional cohorts 5 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.635	AC:1487	Hom:462	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.576	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.647	AC:194	Hom:	AN:300	Cov:
Korea4K (4,157 Koreans)	AF: 0.520	AC:3758	Hom:	AN:7232	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.603	AC:5404	Hom:1631	AN:8960	Cov:

Showing 9 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	6.9
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
GPN-Star LLR	N/A	-3.1
GPN-Star score	N/A	3.1
PhyloP100	Benign	1.1

Showing 6 of 6 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs657152;

hg19: chr9-136139265;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar