rs760061

Positions:

• chr21-35682209-T-C

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-587-27334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,070 control chromosomes in the GnomAD database, including 9,418 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 0.34 (9418 hom., cov: 31)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.532

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000475045.6	c.-587-27334A>G		intron_variant		5		ENSP00000477072

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52238 AN: 151952 Hom.: 9395 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.366

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

GnomAD4 genome AF: 0.344 AC: 52313 AN: 152070 Hom.: 9418 Cov.: 31 AF XY: 0.340 AC XY: 25309 AN XY: 74332

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.353

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.366

Alfa AF: 0.387 Hom.: 7318

Bravo AF: 0.340

Asia WGS AF: 0.221 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.8
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs760061; hg19: chr21-37054507;