rs8134380

Variant names:

• chr21-34849842-T-A
• rs8134380
• NM_001754.5:c.613+9632A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-34849842-T-A
• chr21-34849842-T-C
• chr21-34849842-T-G

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+9632A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 151,254 control chromosomes in the GnomAD database, including 31,633 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 0.63 (31633 hom., cov: 30)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 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+9632A>T		intron	N/A	NP_001745.2
	RUNX1	NM_001001890.3		c.532+9632A>T		intron	N/A	NP_001001890.1	Q01196-1
	RUNX1	NM_001122607.2		c.532+9632A>T		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+9632A>T		intron	N/A	ENSP00000501943.1	Q01196-8
	RUNX1	ENST00000300305.7	TSL:1	c.613+9632A>T		intron	N/A	ENSP00000300305.3	Q01196-8
	RUNX1	ENST00000344691.8	TSL:1	c.532+9632A>T		intron	N/A	ENSP00000340690.4	Q01196-1

Frequencies

GnomAD3 genomes AF: 0.635 AC: 95969 AN: 151178 Hom.: 31609 Cov.: 30

Gnomad AFR AF: 0.823

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.555

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.606

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.635 AC: 96031 AN: 151254 Hom.: 31633 Cov.: 30 AF XY: 0.631 AC XY: 46619 AN XY: 73870

African (AFR) AF: 0.824 AC: 34007 AN: 41294

American (AMR) AF: 0.665 AC: 10120 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 1922 AN: 3464

East Asian (EAS) AF: 0.518 AC: 2658 AN: 5134

South Asian (SAS) AF: 0.536 AC: 2562 AN: 4782

European-Finnish (FIN) AF: 0.511 AC: 5256 AN: 10278

Middle Eastern (MID) AF: 0.608 AC: 174 AN: 286

European-Non Finnish (NFE) AF: 0.553 AC: 37462 AN: 67796

Other (OTH) AF: 0.630 AC: 1317 AN: 2092

Alfa AF: 0.603 Hom.: 3510

Bravo AF: 0.659

Asia WGS AF: 0.573 AC: 1990 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		0.023

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: rs8134380; hg19: chr21-36222139;