rs2835173

Positions:

• chr21-35943681-T-C
• chr21-35943681-T-A

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-771+26394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,034 control chromosomes in the GnomAD database, including 12,813 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 0.40 (12813 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.35943681T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000475045.6	c.-771+26394A>G		intron_variant		5		ENSP00000477072.1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60818 AN: 151916 Hom.: 12801 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.400 AC: 60869 AN: 152034 Hom.: 12813 Cov.: 32 AF XY: 0.398 AC XY: 29544 AN XY: 74320

Gnomad4 AFR AF: 0.539

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.334

Gnomad4 OTH AF: 0.398

Alfa AF: 0.362 Hom.: 1263

Bravo AF: 0.410

Asia WGS AF: 0.459 AC: 1592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.9
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2835173; hg19: chr21-37315979;