9-133261367-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000538324.2(ABO):c.106G>T(p.Val36Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,594,332 control chromosomes in the GnomAD database, including 51,939 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/5 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5809 hom., cov: 32)
  • Exomes 𝑓: 0.25 (46130 hom.)
• Consequence: ABO ENST00000538324.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.461

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002935797).
• BP6: Variant 9-133261367-C-A is Benign according to our data. Variant chr9-133261367-C-A is described in ClinVar as [Benign]. Clinvar id is 769758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABO	NM_020469.3	c.106G>T	p.Val36Phe	missense_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABO	ENST00000538324.2	c.106G>T	p.Val36Phe	missense_variant	3/9	5		A2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41012 AN: 151998 Hom.: 5803 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.276

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.241

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.248 AC: 357039 AN: 1442216 Hom.: 46130 Cov.: 33 AF XY: 0.244 AC XY: 174731 AN XY: 715164

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.475

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.206

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.270 AC: 41039 AN: 152116 Hom.: 5809 Cov.: 32 AF XY: 0.269 AC XY: 19984 AN XY: 74360

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.276

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.215

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.241

Gnomad4 OTH AF: 0.253

Alfa AF: 0.243 Hom.: 7929

Bravo AF: 0.291

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.82
DEOGEN2	Benign	0.0018	T;.
LIST_S2	Benign	0.46	T;T
MetaRNN	Benign	0.0029	T;T
Sift4G	Benign	0.65	T;T
Vest4		0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs688976; hg19: chr9-136136770;