rs2834719

Positions:

• chr21-34989908-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.58+58934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,034 control chromosomes in the GnomAD database, including 6,765 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 0.25 (6765 hom., cov: 31)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

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]

RUNX1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.58+58934G>A		intron_variant		ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.58+58934G>A		intron_variant			NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37392 AN: 151916 Hom.: 6745 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0880

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.246 AC: 37445 AN: 152034 Hom.: 6765 Cov.: 31 AF XY: 0.244 AC XY: 18111 AN XY: 74324

Gnomad4 AFR AF: 0.505

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0880

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.230

Alfa AF: 0.152 Hom.: 4341

Bravo AF: 0.271

Asia WGS AF: 0.166 AC: 578 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.76
DANN	Benign	0.40

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: rs2834719; hg19: chr21-36362205;