9-133263862-A-T

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong

The ENST00000679909.1(ABO):c.28+11300T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: ENST00000679909.1 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 0.0000263 (AC=4) in the gnomAD database across 152,036 control chromosomes (no homozygotes observed). The grpmax filtering allele frequency (95% CI) is 0.0000117. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000026 (0 hom., cov: 33)
• Consequence: ABO ENST00000679909.1 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: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Very rare in gnomAD for AR/unknown gene (popmax AF < threshold/10) — PM2; GnomAD popmax AF = 0.0000117 — very rare for unknown gene (threshold 0.001) — PM2 moderate.
	BP4Computational evidence suggests no impact		Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: ENST00000679909.1. 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>A	intron	Intron 1 of 6	Prot:

ABO NR_198898.1

HGVSc / HGVSpn.41-1694T>A

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>A	intron	Intron 1 of 7	Prot: ENSP00000483265.1 UniProt:
	ABO ENST00000453660.4	TSL:1	n.59-1694T>A	intron	Intron 1 of 6	Prot:
	ABO ENST00000538324.2	TSL:5	c.29-1694T>A	intron	Intron 1 of 8	Prot: ENSP00000483018.1 UniProt:
	ABO ENST00000679909.1		c.28+11300T>A	intron	Intron 1 of 1	Prot: ENSP00000506089.1 UniProt:
	ABO ENST00000647353.1		n.53+11300T>A	intron	Intron 1 of 1	Prot:
	ABO ENST00000651471.1		n.64-1694T>A	intron	Intron 1 of 5	Prot:

ABO ENST00000611156.4

TSL:5

HGVSc / HGVSpc.29-1694T>A

Exon rankIntron 1 of 7

intron

Prot: ENSP00000483265.1UniProt: A0A087X0C2

ABO ENST00000453660.4

TSL:1

HGVSc / HGVSpn.59-1694T>A

Exon rankIntron 1 of 6

intron

Prot:

ABO ENST00000538324.2

TSL:5

HGVSc / HGVSpc.29-1694T>A

Exon rankIntron 1 of 8

intron

Prot: ENSP00000483018.1UniProt: A0A087X009

ABO ENST00000679909.1

HGVSc / HGVSpc.28+11300T>A

Exon rankIntron 1 of 1

intron

Prot: ENSP00000506089.1UniProt: A0A7P0TA91

ABO ENST00000647353.1

HGVSc / HGVSpn.53+11300T>A

Exon rankIntron 1 of 1

intron

Prot:

ABO ENST00000651471.1

HGVSc / HGVSpn.64-1694T>A

Exon rankIntron 1 of 5

intron

Prot:

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: 0.0000263	AC:4	Hom:0	AN:152036	Cov:33
GnomAD4 genome	AF: 0.0000263	AC:4	Hom:0	AN:152036	Cov:33
TOPMed (Bravo)	AF: 0.0000945	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.00	AC:0	Hom:125771	AN:638864	Cov:
Local & regional cohorts 1 source Population-specific and national genomic databases
UK10K	AF: 0.000529	AC:4	Hom:	AN:7562	Cov:

Showing 5 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	7.4
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
GPN-Star LLR	N/A	-3.0
GPN-Star score	N/A	3.0
PhyloP100	Benign	1.1

Showing 6 of 6 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.040
SpliceAI score (max)	Benign	0.0	Details are displayed if max score is > 0.2

Showing 2 of 2 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