rs2268288

Variant names:

• chr21-34860374-T-C
• rs2268288
• NM_001754.5:c.509-796A>G

Variant summary

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

The NM_001754.5(RUNX1):​c.509-796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,150 control chromosomes in the GnomAD database, including 5,078 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 0.24 (5078 hom., cov: 33)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 5 publications found

Genes affected

RUNX1 (HGNC:10471): (RUNX family transcription factor 1) Core binding factor (CBF) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. The protein encoded by this gene represents the alpha subunit of CBF and is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RUNX1-AS1 (HGNC:56821): (RUNX1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001754.5. 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
	RUNX1	NM_001754.5	MANE Select	c.509-796A>G		intron	N/A	NP_001745.2
	RUNX1	NM_001001890.3		c.428-796A>G		intron	N/A	NP_001001890.1
	RUNX1	NM_001122607.2		c.428-796A>G		intron	N/A	NP_001116079.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000675419.1	MANE Select	c.509-796A>G		intron	N/A	ENSP00000501943.1
	RUNX1	ENST00000300305.7	TSL:1	c.509-796A>G		intron	N/A	ENSP00000300305.3
	RUNX1	ENST00000344691.8	TSL:1	c.428-796A>G		intron	N/A	ENSP00000340690.4

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37098 AN: 152032 Hom.: 5074 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.244 AC: 37127 AN: 152150 Hom.: 5078 Cov.: 33 AF XY: 0.239 AC XY: 17813 AN XY: 74400

African (AFR) AF: 0.379 AC: 15717 AN: 41468

American (AMR) AF: 0.159 AC: 2436 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3470

East Asian (EAS) AF: 0.123 AC: 637 AN: 5184

South Asian (SAS) AF: 0.211 AC: 1016 AN: 4822

European-Finnish (FIN) AF: 0.153 AC: 1620 AN: 10590

Middle Eastern (MID) AF: 0.390 AC: 113 AN: 290

European-Non Finnish (NFE) AF: 0.207 AC: 14064 AN: 68000

Other (OTH) AF: 0.235 AC: 497 AN: 2114

Alfa AF: 0.213 Hom.: 7853

Bravo AF: 0.249

Asia WGS AF: 0.195 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.67
PhyloP100		-1.7

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: rs2268288; hg19: chr21-36232671;