21-34938113-C-T

Variant summary

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

The NM_001754.5(RUNX1):c.59-45150G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,142 control chromosomes in the GnomAD database, including 5,770 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 (5770 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX1	NM_001754.5	c.59-45150G>A		intron_variant		ENST00000675419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000675419.1	c.59-45150G>A		intron_variant			NM_001754.5	A1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28441 AN: 152022 Hom.: 5753 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.0851

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0441

Gnomad OTH AF: 0.164

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

GnomAD4 genome AF: 0.187 AC: 28491 AN: 152142 Hom.: 5770 Cov.: 32 AF XY: 0.185 AC XY: 13755 AN XY: 74384

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0577

Gnomad4 EAS AF: 0.0852

Gnomad4 SAS AF: 0.0806

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.0441

Gnomad4 OTH AF: 0.162

Alfa AF: 0.0442 Hom.: 112

Bravo AF: 0.209

Asia WGS AF: 0.119 AC: 412 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.041
Dann	Benign	0.23

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: rs2834681; hg19: chr21-36310410;