chr9-133256085-A-T

Variant names:

• chr9-133256085-A-T
• rs8176740
• ENST00000611156.4:c.643T>A

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.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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 5.15
• Publications: 92 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=0.0047952533).
• 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.

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.657T>A		non_coding_transcript_exon	Exon 7 of 7

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABO	ENST00000611156.4	TSL:5	c.643T>A	p.Phe215Ile	missense	Exon 8 of 8	ENSP00000483265.1
	ABO	ENST00000453660.4	TSL:1	n.675T>A		non_coding_transcript_exon	Exon 7 of 7
	ABO	ENST00000538324.2	TSL:5	c.643T>A	p.Phe215Ile	missense	Exon 8 of 9	ENSP00000483018.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38057 AN: 151686 Hom.: 5118 Cov.: 33

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

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.: 72 AF XY: 0.239 AC XY: 170641 AN XY: 712918

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

GnomAD4 genome AF: 0.251 AC: 38079 AN: 151804 Hom.: 5124 Cov.: 33 AF XY: 0.251 AC XY: 18625 AN XY: 74208

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: 74 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16293 AN: 67884

Other (OTH) AF: 0.243 AC: 512 AN: 2108

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.64
DEOGEN2	Benign	0.28	T
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.75	T
MetaRNN	Benign	0.0048	T
PhyloP100		5.1
PrimateAI	Uncertain	0.59	T
Sift4G	Uncertain	0.0020	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

Other links and lift over

dbSNP: rs8176740; hg19: chr9-136131472; COSMIC: COSV71743541;