rs2834655

Variant names:

• chr21-34866210-G-A
• rs2834655
• NM_001754.5:c.509-6632C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001754.5(RUNX1):​c.509-6632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,124 control chromosomes in the GnomAD database, including 6,200 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 0.28 (6200 hom., cov: 33)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 12 publications found

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-AS1 (HGNC:56821): (RUNX1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.509-6632C>T		intron_variant	Intron 5 of 8	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.509-6632C>T		intron_variant	Intron 5 of 8		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42387 AN: 152006 Hom.: 6195 Cov.: 33

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.279 AC: 42419 AN: 152124 Hom.: 6200 Cov.: 33 AF XY: 0.274 AC XY: 20347 AN XY: 74366

African (AFR) AF: 0.326 AC: 13553 AN: 41518

American (AMR) AF: 0.191 AC: 2915 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1032 AN: 3470

East Asian (EAS) AF: 0.121 AC: 628 AN: 5174

South Asian (SAS) AF: 0.208 AC: 1002 AN: 4828

European-Finnish (FIN) AF: 0.282 AC: 2979 AN: 10574

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19466 AN: 67952

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.277 Hom.: 19061

Bravo AF: 0.272

Asia WGS AF: 0.167 AC: 585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.5
DANN	Benign	0.80
PhyloP100		-0.057

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

Other links and lift over

dbSNP: rs2834655; hg19: chr21-36238507;