rs2834812

Positions:

• chr21-35161365-C-T

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-196-96293G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0524 in 152,302 control chromosomes in the GnomAD database, including 323 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 0.052 (323 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 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.-196-96293G>A		intron_variant		5		ENSP00000477072

Frequencies

GnomAD3 genomes AF: 0.0525 AC: 7983 AN: 152184 Hom.: 323 Cov.: 32

Gnomad AFR AF: 0.0617

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0829

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0524 AC: 7982 AN: 152302 Hom.: 323 Cov.: 32 AF XY: 0.0528 AC XY: 3931 AN XY: 74492

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.0827

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0317

Gnomad4 OTH AF: 0.0497

Alfa AF: 0.0388 Hom.: 383

Bravo AF: 0.0582

Asia WGS AF: 0.128 AC: 442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.38
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834812; hg19: chr21-36533662;