16-88901029-T-C

Variant names:

• chr16-88901029-T-C
• rs533581
• NM_005187.6:c.304+475A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005187.6(CBFA2T3):​c.304+475A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,248 control chromosomes in the GnomAD database, including 13,916 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 0.42 (13916 hom., cov: 35)
• Consequence: CBFA2T3 NM_005187.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.32
• Publications: 11 publications found

Genes affected

CBFA2T3 (HGNC:1537): (CBFA2/RUNX1 partner transcriptional co-repressor 3) This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(16;21)(q24;q22) translocation is one of the less common karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. This gene is also a putative breast tumor suppressor. Alternative splicing results in transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005187.6. 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
	CBFA2T3	NM_005187.6	MANE Select	c.304+475A>G		intron	N/A	NP_005178.4
	CBFA2T3	NM_175931.3		c.121+475A>G		intron	N/A	NP_787127.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CBFA2T3	ENST00000268679.9	TSL:1 MANE Select	c.304+475A>G		intron	N/A	ENSP00000268679.4
	CBFA2T3	ENST00000327483.9	TSL:1	c.121+475A>G		intron	N/A	ENSP00000332122.5
	CBFA2T3	ENST00000569464.5	TSL:1	c.121+475A>G		intron	N/A	ENSP00000454851.1

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63200 AN: 152130 Hom.: 13885 Cov.: 35

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.416 AC: 63279 AN: 152248 Hom.: 13916 Cov.: 35 AF XY: 0.406 AC XY: 30202 AN XY: 74430

African (AFR) AF: 0.552 AC: 22929 AN: 41546

American (AMR) AF: 0.362 AC: 5534 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1381 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1567 AN: 5174

South Asian (SAS) AF: 0.376 AC: 1816 AN: 4826

European-Finnish (FIN) AF: 0.249 AC: 2642 AN: 10610

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26157 AN: 67994

Other (OTH) AF: 0.391 AC: 828 AN: 2116

Alfa AF: 0.406 Hom.: 1617

Bravo AF: 0.429

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.098
DANN	Benign	0.38
PhyloP100		-3.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs533581; hg19: chr16-88967437;