ENST00000611156.4:c.220C>T

Variant names:

• chr9-133258116-G-A
• rs512770
• ENST00000611156.4:c.220C>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.220C>T​(p.Pro74Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 1,613,350 control chromosomes in the GnomAD database, including 41,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4739 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36790 hom.)
• Consequence: ABO ENST00000611156.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.22
• Publications: 63 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=0.0024269521).
• BP6: Variant 9-133258116-G-A is Benign according to our data. Variant chr9-133258116-G-A is described in ClinVar as Benign. ClinVar VariationId is 769757.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABO	NR_198898.1	n.232C>T		non_coding_transcript_exon_variant	Exon 5 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABO	ENST00000611156.4	c.220C>T	p.Pro74Ser	missense_variant	Exon 5 of 8	5		ENSP00000483265.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36421 AN: 151908 Hom.: 4732 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.233

GnomAD4 exome AF: 0.216 AC: 316290 AN: 1461324 Hom.: 36790 Cov.: 32 AF XY: 0.214 AC XY: 155817 AN XY: 726962

African (AFR) AF: 0.267 AC: 8922 AN: 33456

American (AMR) AF: 0.470 AC: 21006 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6620 AN: 26134

East Asian (EAS) AF: 0.258 AC: 10244 AN: 39694

South Asian (SAS) AF: 0.209 AC: 18016 AN: 86246

European-Finnish (FIN) AF: 0.151 AC: 8027 AN: 53308

Middle Eastern (MID) AF: 0.244 AC: 1409 AN: 5766

European-Non Finnish (NFE) AF: 0.205 AC: 228243 AN: 1111690

Other (OTH) AF: 0.229 AC: 13803 AN: 60364

GnomAD4 genome AF: 0.240 AC: 36446 AN: 152026 Hom.: 4739 Cov.: 32 AF XY: 0.240 AC XY: 17827 AN XY: 74326

African (AFR) AF: 0.265 AC: 10961 AN: 41366

American (AMR) AF: 0.377 AC: 5766 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1395 AN: 5168

South Asian (SAS) AF: 0.218 AC: 1049 AN: 4816

European-Finnish (FIN) AF: 0.154 AC: 1631 AN: 10598

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

European-Non Finnish (NFE) AF: 0.208 AC: 14117 AN: 68008

Other (OTH) AF: 0.232 AC: 491 AN: 2114

Alfa AF: 0.222 Hom.: 14307

Bravo AF: 0.261

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 v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
CADD	Benign	20
DEOGEN2	Benign	0.10	T;.
LIST_S2	Benign	0.70	T;T
MetaRNN	Benign	0.0024	T;T
PhyloP100		2.2
Sift4G	Benign	0.068	T;T
Vest4		0.21
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.52

Splicing

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

Other links and lift over

dbSNP: rs512770; hg19: -;