rs2834643

Positions:

• chr21-34814099-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001754.5(RUNX1):​c.806-14637T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 152,032 control chromosomes in the GnomAD database, including 13,579 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 0.42 (13579 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.806-14637T>C		intron_variant		ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.806-14637T>C		intron_variant			NM_001754.5	ENSP00000501943	A1

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64055 AN: 151914 Hom.: 13570 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.382

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.422 AC: 64113 AN: 152032 Hom.: 13579 Cov.: 32 AF XY: 0.421 AC XY: 31323 AN XY: 74314

Gnomad4 AFR AF: 0.433

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.414

Alfa AF: 0.425 Hom.: 3415

Bravo AF: 0.424

Asia WGS AF: 0.419 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834643; hg19: chr21-36186396;