rs2300395

Variant names:

• chr21-34872901-C-T
• rs2300395
• NM_001754.5:c.508+7656G>A

Variant summary

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

The NM_001754.5(RUNX1):​c.508+7656G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,002 control chromosomes in the GnomAD database, including 18,808 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 0.43 (18808 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001754.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	NM_001754.5	MANE Select	c.508+7656G>A		intron	N/A	NP_001745.2
	RUNX1	NM_001001890.3		c.427+7656G>A		intron	N/A	NP_001001890.1
	RUNX1	NM_001122607.2		c.427+7656G>A		intron	N/A	NP_001116079.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000675419.1	MANE Select	c.508+7656G>A		intron	N/A	ENSP00000501943.1
	RUNX1	ENST00000300305.7	TSL:1	c.508+7656G>A		intron	N/A	ENSP00000300305.3
	RUNX1	ENST00000344691.8	TSL:1	c.427+7656G>A		intron	N/A	ENSP00000340690.4

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65384 AN: 151882 Hom.: 18752 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.431 AC: 65503 AN: 152002 Hom.: 18808 Cov.: 32 AF XY: 0.423 AC XY: 31420 AN XY: 74276

African (AFR) AF: 0.826 AC: 34267 AN: 41462

American (AMR) AF: 0.256 AC: 3916 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 944 AN: 3466

East Asian (EAS) AF: 0.161 AC: 831 AN: 5158

South Asian (SAS) AF: 0.319 AC: 1536 AN: 4810

European-Finnish (FIN) AF: 0.243 AC: 2565 AN: 10542

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20201 AN: 67968

Other (OTH) AF: 0.376 AC: 794 AN: 2110

Alfa AF: 0.328 Hom.: 30464

Bravo AF: 0.445

Asia WGS AF: 0.268 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.44
PhyloP100		-0.81

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: rs2300395; hg19: chr21-36245198;