rs4816502

Variant names:

• chr21-34991231-C-A
• rs4816502
• NM_001754.5:c.58+57611G>T

Your query was ambiguous. Multiple possible variants found:

• chr21-34991231-C-A
• chr21-34991231-C-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+57611G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,134 control chromosomes in the GnomAD database, including 5,278 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 (5278 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 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+57611G>T		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+57611G>T		intron	N/A	ENSP00000501943.1
	RUNX1	ENST00000300305.7	TSL:1	c.58+57611G>T		intron	N/A	ENSP00000300305.3
	RUNX1	ENST00000416754.1	TSL:1	c.58+57611G>T		intron	N/A	ENSP00000405158.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36722 AN: 152016 Hom.: 5281 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.318

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.241 AC: 36723 AN: 152134 Hom.: 5278 Cov.: 32 AF XY: 0.242 AC XY: 17996 AN XY: 74364

African (AFR) AF: 0.0842 AC: 3496 AN: 41540

American (AMR) AF: 0.206 AC: 3154 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1202 AN: 3468

East Asian (EAS) AF: 0.387 AC: 1994 AN: 5156

South Asian (SAS) AF: 0.318 AC: 1530 AN: 4812

European-Finnish (FIN) AF: 0.299 AC: 3169 AN: 10596

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21214 AN: 67954

Other (OTH) AF: 0.262 AC: 553 AN: 2112

Alfa AF: 0.298 Hom.: 4157

Bravo AF: 0.226

Asia WGS AF: 0.370 AC: 1285 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.80
PhyloP100		-0.028

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: rs4816502; hg19: chr21-36363528;