rs2834664

Positions:

• chr21-34903142-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.59-10179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,138 control chromosomes in the GnomAD database, including 3,892 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 0.19 (3892 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.03

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.59-10179A>G		intron_variant		ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.59-10179A>G		intron_variant			NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29045 AN: 152020 Hom.: 3885 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0432

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.191 AC: 29091 AN: 152138 Hom.: 3892 Cov.: 32 AF XY: 0.188 AC XY: 13991 AN XY: 74376

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.141

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.0432

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.170

Alfa AF: 0.140 Hom.: 2301

Bravo AF: 0.199

Asia WGS AF: 0.171 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.57

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: rs2834664; hg19: chr21-36275439;