Genetic Variant ABO:p.Phe215Ile (chr9-133256085-A-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000611156.4(ABO):c.643T>A(p.Phe215Ile) variant causes a missense change. The variant allele was found at a frequency of 0.243 in 1,588,528 control chromosomes in the GnomAD database, including 49,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5124 hom., cov: 33)

Exomes 𝑓: 0.24 ( 44060 hom. )

Consequence

ABO
ENST00000611156.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.15

Publications

92 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047952533).

BP6

Variant 9-133256085-A-T is Benign according to our data. Variant chr9-133256085-A-T is described in ClinVar as Benign. ClinVar VariationId is 812632.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1 link	n.657T>A		non_coding_transcript_exon_variant	Exon 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4 link	c.643T>A	p.Phe215Ile	missense_variant	Exon 8 of 8	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38057

AN:

151686

Hom.:

5118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.277

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.247

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.244

GnomAD2 exomes

AF:

0.253

AC:

52729

AN:

208400

AF XY:

0.241

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.172

Gnomad NFE exome

AF:

0.221

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.243

AC:

348446

AN:

1436724

Hom.:

44060

Cov.:

AF XY:

0.239

AC XY:

170641

AN XY:

712918

show subpopulations

African (AFR)

AF:

0.240

AC:

7873

AN:

32756

American (AMR)

AF:

0.455

AC:

18171

AN:

39896

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

7090

AN:

25600

East Asian (EAS)

AF:

0.254

AC:

9669

AN:

38018

South Asian (SAS)

AF:

0.202

AC:

16799

AN:

83208

European-Finnish (FIN)

AF:

0.175

AC:

9022

AN:

51530

Middle Eastern (MID)

AF:

0.232

AC:

1328

AN:

5736

European-Non Finnish (NFE)

AF:

0.239

AC:

263563

AN:

1100476

Other (OTH)

AF:

0.251

AC:

14931

AN:

59504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

17690

35380

53071

70761

88451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9200

18400

27600

36800

46000

<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:

0.251

AC:

38079

AN:

151804

Hom.:

5124

Cov.:

AF XY:

0.251

AC XY:

18625

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.243

AC:

10065

AN:

41336

American (AMR)

AF:

0.380

AC:

5798

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.277

AC:

958

AN:

3464

East Asian (EAS)

AF:

0.268

AC:

1375

AN:

5130

South Asian (SAS)

AF:

0.211

AC:

1018

AN:

4818

European-Finnish (FIN)

AF:

0.179

AC:

1892

AN:

10596

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.240

AC:

16293

AN:

67884

Other (OTH)

AF:

0.243

AC:

512

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1471

2942

4412

5883

7354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.244

Hom.:

1638

Bravo

AF:

0.269

TwinsUK

AF:

0.238

AC:

883

ALSPAC

AF:

0.247

AC:

953

ESP6500AA

AF:

0.221

AC:

958

ESP6500EA

AF:

0.229

AC:

1946

ExAC

AF:

0.213

AC:

25437

Asia WGS

AF:

0.261

AC:

907

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Three Vessel Coronary Disease

Benign:1

Department of Cardiology, Chinese Academy of Medical Sciences, Fuwai Hospital

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.75

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.28

T;.

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.75

T;T

MetaRNN

Benign

0.0048

T;T

MutationAssessor

Benign

0.0

.;.

PhyloP100

5.1

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.0

.;.

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;.

Sift4G

Uncertain

0.0020

D;D

Vest4

0.41

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.62

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over