Genetic Variant ENST00000611156.4:c.654C>T (chr9-133256074-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000611156.4(ABO):c.654C>T(p.His218His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 1,588,890 control chromosomes in the GnomAD database, including 9,425 homozygotes. In-silico tool predicts 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: 33)

Exomes 𝑓: 0.089 ( 8127 hom. )

Consequence

ABO
ENST00000611156.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.194

Publications

81 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=-0.194 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.245 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.668C>T		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
ABO	ENST00000611156.4	TSL:5	c.654C>T	p.His218His	synonymous	Exon 8 of 8	ENSP00000483265.1
ABO	ENST00000453660.4	TSL:1	n.686C>T		non_coding_transcript_exon	Exon 7 of 7
ABO	ENST00000538324.2	TSL:5	c.654C>T	p.His218His	synonymous	Exon 8 of 9	ENSP00000483018.1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17529

AN:

151920

Hom.:

1296

Cov.:

show subpopulations

Gnomad AFR

AF:

0.159

Gnomad AMI

AF:

0.0800

Gnomad AMR

AF:

0.0740

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0798

Gnomad OTH

AF:

0.105

GnomAD2 exomes

AF:

0.119

AC:

24772

AN:

207772

AF XY:

0.127

show subpopulations

Gnomad AFR exome

AF:

0.170

Gnomad AMR exome

AF:

0.0571

Gnomad ASJ exome

AF:

0.121

Gnomad EAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.0775

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.0892

AC:

128163

AN:

1436852

Hom.:

8127

Cov.:

AF XY:

0.0948

AC XY:

67607

AN XY:

712938

show subpopulations

African (AFR)

AF:

0.166

AC:

5428

AN:

32778

American (AMR)

AF:

0.0569

AC:

2274

AN:

39976

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

3187

AN:

25596

East Asian (EAS)

AF:

0.181

AC:

6883

AN:

37980

South Asian (SAS)

AF:

0.260

AC:

21593

AN:

83082

European-Finnish (FIN)

AF:

0.135

AC:

6968

AN:

51522

Middle Eastern (MID)

AF:

0.150

AC:

862

AN:

5736

European-Non Finnish (NFE)

AF:

0.0680

AC:

74860

AN:

1100708

Other (OTH)

AF:

0.103

AC:

6108

AN:

59474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

7803

15607

23410

31214

39017

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2848

5696

8544

11392

14240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.115

AC:

17543

AN:

152038

Hom.:

1298

Cov.:

AF XY:

0.120

AC XY:

8883

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.159

AC:

6569

AN:

41398

American (AMR)

AF:

0.0741

AC:

1133

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

465

AN:

3472

East Asian (EAS)

AF:

0.183

AC:

942

AN:

5154

South Asian (SAS)

AF:

0.257

AC:

1238

AN:

4824

European-Finnish (FIN)

AF:

0.137

AC:

1452

AN:

10612

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0798

AC:

5427

AN:

67972

Other (OTH)

AF:

0.104

AC:

220

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

785

1570

2355

3140

3925

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

214

428

642

856

1070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0885

Hom.:

1708

Bravo

AF:

0.106

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

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.6

(source)

DANN

Benign

0.86

PhyloP100

-0.19

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over