rs9979015

Variant names:

• chr21-34863271-C-A
• rs9979015
• NM_001754.5:c.509-3693G>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.509-3693G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,068 control chromosomes in the GnomAD database, including 8,290 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 0.29 (8290 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.532 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.509-3693G>T		intron	N/A	NP_001745.2
	RUNX1	NM_001001890.3		c.428-3693G>T		intron	N/A	NP_001001890.1
	RUNX1	NM_001122607.2		c.428-3693G>T		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.509-3693G>T		intron	N/A	ENSP00000501943.1
	RUNX1	ENST00000300305.7	TSL:1	c.509-3693G>T		intron	N/A	ENSP00000300305.3
	RUNX1	ENST00000344691.8	TSL:1	c.428-3693G>T		intron	N/A	ENSP00000340690.4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44242 AN: 151950 Hom.: 8262 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.291 AC: 44312 AN: 152068 Hom.: 8290 Cov.: 32 AF XY: 0.284 AC XY: 21152 AN XY: 74360

African (AFR) AF: 0.537 AC: 22265 AN: 41424

American (AMR) AF: 0.190 AC: 2905 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1066 AN: 3472

East Asian (EAS) AF: 0.119 AC: 618 AN: 5182

South Asian (SAS) AF: 0.192 AC: 924 AN: 4816

European-Finnish (FIN) AF: 0.153 AC: 1617 AN: 10588

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14070 AN: 67992

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.230 Hom.: 7743

Bravo AF: 0.303

Asia WGS AF: 0.183 AC: 641 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		0.24

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: rs9979015; hg19: chr21-36235568;