chr21-34990282-T-C

Variant names:

• chr21-34990282-T-C
• rs2242878
• NM_001754.5:c.58+58560A>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.58+58560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 152,210 control chromosomes in the GnomAD database, including 55,165 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 0.85 (55165 hom., cov: 31)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 8 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 Gene-Disease associations (from GenCC):

• hereditary thrombocytopenia and hematologic cancer predisposition syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 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.58+58560A>G		intron	N/A	NP_001745.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000675419.1	MANE Select	c.58+58560A>G		intron	N/A	ENSP00000501943.1
	RUNX1	ENST00000300305.7	TSL:1	c.58+58560A>G		intron	N/A	ENSP00000300305.3
	RUNX1	ENST00000416754.1	TSL:1	c.58+58560A>G		intron	N/A	ENSP00000405158.1

Frequencies

GnomAD3 genomes AF: 0.848 AC: 128979 AN: 152092 Hom.: 55118 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.759

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.853

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

GnomAD4 genome AF: 0.848 AC: 129081 AN: 152210 Hom.: 55165 Cov.: 31 AF XY: 0.844 AC XY: 62800 AN XY: 74404

African (AFR) AF: 0.961 AC: 39913 AN: 41542

American (AMR) AF: 0.828 AC: 12664 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3850 AN: 5166

South Asian (SAS) AF: 0.752 AC: 3626 AN: 4824

European-Finnish (FIN) AF: 0.759 AC: 8032 AN: 10588

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.813 AC: 55267 AN: 68010

Other (OTH) AF: 0.853 AC: 1803 AN: 2114

Alfa AF: 0.832 Hom.: 104652

Bravo AF: 0.860

Asia WGS AF: 0.803 AC: 2795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.9
DANN	Benign	0.76
PhyloP100		0.025

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: rs2242878; hg19: chr21-36362579;