rs2834819

chr21-35171631-C-T

Variant summary

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

The ENST00000475045.6(RUNX1):c.-196-106559G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,022 control chromosomes in the GnomAD database, including 26,616 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 0.55 (26616 hom., cov: 31)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 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.-196-106559G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83991 AN: 151904 Hom.: 26562 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.405

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.435

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.553 AC: 84096 AN: 152022 Hom.: 26616 Cov.: 31 AF XY: 0.545 AC XY: 40463 AN XY: 74282

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.405

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.435

Gnomad4 OTH AF: 0.525

Alfa AF: 0.460 Hom.: 16282

Bravo AF: 0.577

Asia WGS AF: 0.459 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.0060
Dann	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834819; hg19: chr21-36543928;