rs2268288

Positions:

• chr21-34860374-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.509-796A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,150 control chromosomes in the GnomAD database, including 5,078 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 (5078 hom., cov: 33)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX1	NM_001754.5	c.509-796A>G		intron_variant		ENST00000675419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000675419.1	c.509-796A>G		intron_variant			NM_001754.5	A1
RUNX1-AS1	ENST00000651798.1	n.662-23109T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37098 AN: 152032 Hom.: 5074 Cov.: 33

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.244 AC: 37127 AN: 152150 Hom.: 5078 Cov.: 33 AF XY: 0.239 AC XY: 17813 AN XY: 74400

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.235

Alfa AF: 0.211 Hom.: 5545

Bravo AF: 0.249

Asia WGS AF: 0.195 AC: 681 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.67

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: rs2268288; hg19: chr21-36232671;