rs6120328

Positions:

• chr20-33612066-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001032999.3(CBFA2T2):​c.420+731G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 152,046 control chromosomes in the GnomAD database, including 27,267 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.58 (27267 hom., cov: 32)
• Consequence: CBFA2T2 NM_001032999.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74

Genes affected

CBFA2T2 (HGNC:1536): (CBFA2/RUNX1 partner transcriptional co-repressor 2) In acute myeloid leukemia, especially in the M2 subtype, the t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities. The translocation produces a chimeric gene made up of the 5'-region of the RUNX1 (AML1) gene fused to the 3'-region of the CBFA2T1 (MTG8) gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. The protein encoded by this gene binds to the AML1-MTG8 complex and may be important in promoting leukemogenesis. Several transcript variants are thought to exist for this gene, but the full-length natures of only three have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CBFA2T2	NM_001032999.3	c.420+731G>A		intron_variant		ENST00000342704.11	NP_001028171.1
CBFA2T2	NM_001039709.2	c.360+731G>A		intron_variant			NP_001034798.1
CBFA2T2	NM_005093.4	c.447+731G>A		intron_variant			NP_005084.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CBFA2T2	ENST00000342704.11	c.420+731G>A		intron_variant		1	NM_001032999.3	ENSP00000345810	P4

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88446 AN: 151928 Hom.: 27224 Cov.: 32

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.582 AC: 88537 AN: 152046 Hom.: 27267 Cov.: 32 AF XY: 0.582 AC XY: 43266 AN XY: 74302

Gnomad4 AFR AF: 0.782

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.556

Alfa AF: 0.508 Hom.: 5727

Bravo AF: 0.601

Asia WGS AF: 0.643 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.014
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs6120328; hg19: chr20-32199872;