rs9979153

chr21-34951210-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.59-58247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0694 in 152,228 control chromosomes in the GnomAD database, including 507 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 0.069 (507 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX1	NM_001754.5	c.59-58247G>A		intron_variant		ENST00000675419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000675419.1	c.59-58247G>A		intron_variant			NM_001754.5	A1

Frequencies

GnomAD3 genomes AF: 0.0694 AC: 10560 AN: 152110 Hom.: 507 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.0328

Gnomad FIN AF: 0.0670

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.0680

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

GnomAD4 genome AF: 0.0694 AC: 10563 AN: 152228 Hom.: 507 Cov.: 32 AF XY: 0.0696 AC XY: 5178 AN XY: 74418

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.0910

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0533

Gnomad4 SAS AF: 0.0332

Gnomad4 FIN AF: 0.0670

Gnomad4 NFE AF: 0.0405

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0477 Hom.: 120

Bravo AF: 0.0755

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.9
Dann	Benign	0.61

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: rs9979153; hg19: chr21-36323507;