chr9-133261367-C-A

Variant names:

• chr9-133261367-C-A
• rs688976
• ENST00000611156.4:c.106G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000611156.4(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. 5/6 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 ENST00000611156.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.461
• Publications: 50 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

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.118G>T		non_coding_transcript_exon	Exon 3 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.106G>T	p.Val36Phe	missense	Exon 3 of 8	ENSP00000483265.1
	ABO	ENST00000453660.4	TSL:1	n.136G>T		non_coding_transcript_exon	Exon 3 of 7
	ABO	ENST00000538324.2	TSL:5	c.106G>T	p.Val36Phe	missense	Exon 3 of 9	ENSP00000483018.1

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

African (AFR) AF: 0.310 AC: 10219 AN: 33006

American (AMR) AF: 0.475 AC: 19940 AN: 42016

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 7192 AN: 25766

East Asian (EAS) AF: 0.260 AC: 10094 AN: 38824

South Asian (SAS) AF: 0.206 AC: 17035 AN: 82606

European-Finnish (FIN) AF: 0.178 AC: 9290 AN: 52148

Middle Eastern (MID) AF: 0.235 AC: 1352 AN: 5748

European-Non Finnish (NFE) AF: 0.242 AC: 266546 AN: 1102372

Other (OTH) AF: 0.257 AC: 15371 AN: 59730

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

African (AFR) AF: 0.309 AC: 12816 AN: 41464

American (AMR) AF: 0.385 AC: 5890 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 958 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1396 AN: 5160

South Asian (SAS) AF: 0.215 AC: 1035 AN: 4822

European-Finnish (FIN) AF: 0.178 AC: 1885 AN: 10604

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.241 AC: 16354 AN: 67982

Other (OTH) AF: 0.253 AC: 535 AN: 2114

Alfa AF: 0.249 Hom.: 13152

Bravo AF: 0.291

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DEOGEN2	Benign	0.0018	T
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0029	T
PhyloP100		-0.46
Sift4G	Benign	0.65	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

Other links and lift over

dbSNP: rs688976; hg19: chr9-136136770;