21-34843984-A-G

Variant names:

• chr21-34843984-A-G
• rs2268281
• NM_001754.5:c.614-9383T>C

Variant summary

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

The NM_001754.5(RUNX1):​c.614-9383T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,056 control chromosomes in the GnomAD database, including 3,691 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 0.21 (3691 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.46
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.46 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	NM_001754.5	MANE Select	c.614-9383T>C		intron	N/A	NP_001745.2
	RUNX1	NM_001001890.3		c.533-9383T>C		intron	N/A	NP_001001890.1	Q01196-1
	RUNX1	NM_001122607.2		c.533-9383T>C		intron	N/A	NP_001116079.1	Q01196-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000675419.1	MANE Select	c.614-9383T>C		intron	N/A	ENSP00000501943.1	Q01196-8
	RUNX1	ENST00000300305.7	TSL:1	c.614-9383T>C		intron	N/A	ENSP00000300305.3	Q01196-8
	RUNX1	ENST00000344691.8	TSL:1	c.533-9383T>C		intron	N/A	ENSP00000340690.4	Q01196-1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31323 AN: 151938 Hom.: 3690 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.169

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.206 AC: 31365 AN: 152056 Hom.: 3691 Cov.: 32 AF XY: 0.210 AC XY: 15643 AN XY: 74328

African (AFR) AF: 0.233 AC: 9641 AN: 41460

American (AMR) AF: 0.304 AC: 4648 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 466 AN: 3470

East Asian (EAS) AF: 0.476 AC: 2457 AN: 5160

South Asian (SAS) AF: 0.264 AC: 1272 AN: 4814

European-Finnish (FIN) AF: 0.152 AC: 1611 AN: 10600

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.158 AC: 10771 AN: 67974

Other (OTH) AF: 0.200 AC: 421 AN: 2106

Alfa AF: 0.185 Hom.: 4386

Bravo AF: 0.223

Asia WGS AF: 0.375 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.71
PhyloP100		-3.5

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: rs2268281; hg19: chr21-36216281;