NM_001754.5:c.613+1830G>A

Variant names:

• chr21-34857644-C-T
• rs2248383
• NM_001754.5:c.613+1830G>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.613+1830G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 152,214 control chromosomes in the GnomAD database, including 53,187 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 0.83 (53187 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	NM_001754.5	MANE Select	c.613+1830G>A		intron	N/A	NP_001745.2
	RUNX1	NM_001001890.3		c.532+1830G>A		intron	N/A	NP_001001890.1	Q01196-1
	RUNX1	NM_001122607.2		c.532+1830G>A		intron	N/A	NP_001116079.1	Q01196-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000675419.1	MANE Select	c.613+1830G>A		intron	N/A	ENSP00000501943.1	Q01196-8
	RUNX1	ENST00000300305.7	TSL:1	c.613+1830G>A		intron	N/A	ENSP00000300305.3	Q01196-8
	RUNX1	ENST00000344691.8	TSL:1	c.532+1830G>A		intron	N/A	ENSP00000340690.4	Q01196-1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126976 AN: 152096 Hom.: 53145 Cov.: 32

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.875

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.835 AC: 127075 AN: 152214 Hom.: 53187 Cov.: 32 AF XY: 0.839 AC XY: 62417 AN XY: 74434

African (AFR) AF: 0.857 AC: 35585 AN: 41538

American (AMR) AF: 0.872 AC: 13335 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2676 AN: 3472

East Asian (EAS) AF: 0.953 AC: 4941 AN: 5184

South Asian (SAS) AF: 0.820 AC: 3960 AN: 4828

European-Finnish (FIN) AF: 0.875 AC: 9274 AN: 10596

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54583 AN: 67988

Other (OTH) AF: 0.830 AC: 1754 AN: 2114

Alfa AF: 0.812 Hom.: 80362

Bravo AF: 0.836

Asia WGS AF: 0.884 AC: 3074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.047
DANN	Benign	0.50
PhyloP100		-2.0

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: rs2248383; hg19: chr21-36229941;