Genetic Variant ENST00000611156.4:c.29-1694T>G (chr9-133263862-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Publications

268 publications found

Variant links:

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]

ABO links:

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new If you want to explore the variant's impact on the transcript ENST00000611156.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

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

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

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	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ABO	ENST00000611156.4	TSL:5	c.29-1694T>G	intron	N/A	ENSP00000483265.1	A0A087X0C2
ABO	ENST00000453660.4	TSL:1	n.59-1694T>G	intron	N/A
ABO	ENST00000538324.2	TSL:5	c.29-1694T>G	intron	N/A	ENSP00000483018.1	A0A087X009

Frequencies

GnomAD3 genomes

AF:

0.606

AC:

92111

AN:

151982

Hom.:

28165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.697

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.625

Gnomad SAS

AF:

0.551

Gnomad FIN

AF:

0.523

Gnomad MID

AF:

0.642

Gnomad NFE

AF:

0.633

Gnomad OTH

AF:

0.616

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.606

AC:

92180

AN:

152100

Hom.:

28191

Cov.:

AF XY:

0.604

AC XY:

44901

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.563

AC:

23356

AN:

41488

American (AMR)

AF:

0.697

AC:

10657

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1947

AN:

3468

East Asian (EAS)

AF:

0.625

AC:

3236

AN:

5178

South Asian (SAS)

AF:

0.551

AC:

2658

AN:

4824

European-Finnish (FIN)

AF:

0.523

AC:

5517

AN:

10558

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.633

AC:

43034

AN:

67990

Other (OTH)

AF:

0.619

AC:

1306

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1851

3702

5553

7404

9255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.621

AC:

164318

AN:

264690

Hom.:

51563

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.624

AC:

398852

AN:

638864

Hom.:

125771

Local populations

ABraOM SABE-WGS-1171

AF:

0.635

AC:

1487

AN:

2342

Hom.:

462

ChinaMAP Phase 1

AF:

0.576

Denmark Genome

AF:

0.647

AC:

194

AN:

300

Korea4K (4,157 Koreans)

AF:

0.520

AC:

3758

AN:

7232

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.603

AC:

5404

AN:

8960

Hom.:

1631

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.6

(source)

PhyloP100

1.1

AlphaGenome AVI

Benign

6.9

(source)

GPN-Star LLR

-3.1

(source)

GPN-Star score

3.1

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Pangolin (max)

Benign

0.0

(source)

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.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over