rs2248159

Positions:

• chr21-35204304-G-A

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-196-139232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 152,086 control chromosomes in the GnomAD database, including 7,311 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 0.28 (7311 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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 (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000475045.6	c.-196-139232C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41786 AN: 151966 Hom.: 7302 Cov.: 32

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.275 AC: 41833 AN: 152086 Hom.: 7311 Cov.: 32 AF XY: 0.274 AC XY: 20373 AN XY: 74334

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.266

Alfa AF: 0.199 Hom.: 4488

Bravo AF: 0.293

Asia WGS AF: 0.387 AC: 1342 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	0.16
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2248159; hg19: chr21-36576601;