16-88881339-C-T

Variant names:

• chr16-88881339-C-T
• rs201101361
• NM_005187.6:c.1354G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_005187.6(CBFA2T3):​c.1354G>A​(p.Ala452Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,581,246 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: CBFA2T3 NM_005187.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.29
• Publications: 1 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]

ENSG00000259881 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007483572).
• BP6: Variant 16-88881339-C-T is Benign according to our data. Variant chr16-88881339-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3137942.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBFA2T3	NM_005187.6	c.1354G>A	p.Ala452Thr	missense_variant	Exon 9 of 12	ENST00000268679.9	NP_005178.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBFA2T3	ENST00000268679.9	c.1354G>A	p.Ala452Thr	missense_variant	Exon 9 of 12	1	NM_005187.6	ENSP00000268679.4

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152192 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000380 AC: 75 AN: 197152 AF XY: 0.000414

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000332

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00139

Gnomad NFE exome AF: 0.000612

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000300 AC: 429 AN: 1429054 Hom.: 1 Cov.: 32 AF XY: 0.000301 AC XY: 213 AN XY: 708458

African (AFR) AF: 0.0000610 AC: 2 AN: 32782

American (AMR) AF: 0.0000486 AC: 2 AN: 41182

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25522

East Asian (EAS) AF: 0.00 AC: 0 AN: 38184

South Asian (SAS) AF: 0.000120 AC: 10 AN: 83552

European-Finnish (FIN) AF: 0.00142 AC: 65 AN: 45900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.000311 AC: 341 AN: 1097180

Other (OTH) AF: 0.000152 AC: 9 AN: 59042

GnomAD4 genome AF: 0.000191 AC: 29 AN: 152192 Hom.: 0 Cov.: 34 AF XY: 0.000202 AC XY: 15 AN XY: 74352

African (AFR) AF: 0.0000482 AC: 2 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000226 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000246 AC: 2

ExAC AF: 0.000446 AC: 52

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Apr 12, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.047
DANN	Benign	0.73
DEOGEN2	Benign	0.083	.;T;T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.27	T;T;T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.0075	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.41	.;N;.
PhyloP100		-2.3
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.11	N;N;N
REVEL	Benign	0.030
Sift	Benign	0.69	T;T;T
Sift4G	Benign	0.54	T;T;.
Polyphen		0.0	B;B;.
Vest4		0.11
MVP		0.081
MPC		0.062
ClinPred		0.014	T
GERP RS		-10
Varity_R		0.025
gMVP		0.31
Mutation Taster		=99/1	polymorphism

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: rs201101361; hg19: chr16-88947747; COSMIC: COSV105867618;