rs2243988

chr21-34830143-T-C

Variant summary

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

The NM_001754.5(RUNX1):c.805+4267A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,078 control chromosomes in the GnomAD database, including 18,629 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 0.45 (18629 hom., cov: 31)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX1	NM_001754.5	c.805+4267A>G		intron_variant		ENST00000675419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000675419.1	c.805+4267A>G		intron_variant			NM_001754.5	A1

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68817 AN: 151958 Hom.: 18633 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.834

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.508

Gnomad SAS AF: 0.579

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.452 AC: 68810 AN: 152078 Hom.: 18629 Cov.: 31 AF XY: 0.455 AC XY: 33784 AN XY: 74318

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.508

Gnomad4 SAS AF: 0.580

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.485

Alfa AF: 0.541 Hom.: 13338

Bravo AF: 0.427

Asia WGS AF: 0.493 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.0040
Dann	Benign	0.45

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: rs2243988; hg19: chr21-36202440;