Genetic Variant ENST00000611156.4:c.654C>A (chr9-133256074-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000611156.4(ABO):c.654C>A(p.His218Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000696 in 1,436,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H218H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

ABO
ENST00000611156.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.194

Publications

0 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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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.072687685).

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>A		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>A	p.His218Gln	missense	Exon 8 of 8	ENSP00000483265.1
ABO	ENST00000453660.4	TSL:1	n.686C>A		non_coding_transcript_exon	Exon 7 of 7
ABO	ENST00000538324.2	TSL:5	c.654C>A	p.His218Gln	missense	Exon 8 of 9	ENSP00000483018.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.96e-7

AC:

AN:

1436986

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

713026

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32782

American (AMR)

AF:

0.00

AC:

AN:

39978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25596

East Asian (EAS)

AF:

0.00

AC:

AN:

38002

South Asian (SAS)

AF:

0.00

AC:

AN:

83114

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

9.08e-7

AC:

AN:

1100772

Other (OTH)

AF:

0.00

AC:

AN:

59478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.14

FATHMM_MKL

Benign

0.059

LIST_S2

Benign

0.59

MetaRNN

Benign

0.073

PhyloP100

-0.19

PrimateAI

Benign

0.44

Sift4G

Benign

0.079

Vest4

0.17

MVP

0.030

GERP RS

-4.2

gMVP

0.40

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over