rs1883067

chr21-35027879-T-C

Variant summary

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

The NM_001754.5(RUNX1):c.58+20963A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 152,338 control chromosomes in the GnomAD database, including 302 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 0.053 (302 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993

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 (NFE) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX1	NM_001754.5	c.58+20963A>G		intron_variant		ENST00000675419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000675419.1	c.58+20963A>G		intron_variant			NM_001754.5	A1

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8108 AN: 152220 Hom.: 301 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0647

Gnomad ASJ AF: 0.0524

Gnomad EAS AF: 0.00346

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0440

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

GnomAD4 genome AF: 0.0532 AC: 8112 AN: 152338 Hom.: 302 Cov.: 32 AF XY: 0.0546 AC XY: 4069 AN XY: 74498

Gnomad4 AFR AF: 0.0136

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.0524

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0302

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.0701

Gnomad4 OTH AF: 0.0435

Alfa AF: 0.0638 Hom.: 461

Bravo AF: 0.0484

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.41
Dann	Benign	0.36

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: rs1883067; hg19: chr21-36400176;