rs2294163

Positions:

• chr21-35035093-G-A

Variant summary

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

The NM_001754.5(RUNX1):​c.58+13749C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,194 control chromosomes in the GnomAD database, including 2,657 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 0.17 (2657 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX1	NM_001754.5	c.58+13749C>T		intron_variant		ENST00000675419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000675419.1	c.58+13749C>T		intron_variant			NM_001754.5	A1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25540 AN: 152076 Hom.: 2659 Cov.: 32

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.168 AC: 25538 AN: 152194 Hom.: 2657 Cov.: 32 AF XY: 0.175 AC XY: 13024 AN XY: 74398

Gnomad4 AFR AF: 0.0419

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.369

Gnomad4 SAS AF: 0.290

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.197

Gnomad4 OTH AF: 0.178

Alfa AF: 0.199 Hom.: 4115

Bravo AF: 0.160

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.77

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: rs2294163; hg19: chr21-36407390;