rs2298352

Variant names:

• chr21-34880325-T-C
• rs2298352
• NM_001754.5:c.508+232A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP7 BA1 BP4

This summary comes from the ClinGen Evidence Repository: NM_001754.5(RUNX1):c.508+232A>G is an intronic variant with a MAF of 0.31559 (31.559%, 2745/8698, 11,443 alleles) in the African subpopulation of the gnomAD v.2 cohort is ≥ 0.0015 (0.15%) (BA1). Evolutionary conservation algorithms predict the site as not being conserved (PhyloP score -0.537268 < 2.0 or the variant is the reference nucleotide in one primate and/or three mammal species) and splicing is not predicted to be impacted (BP4, BP7). In summary, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: BA1, BP4, BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA14879301/MONDO:0011071/008

• Frequency: Genomes: 𝑓 0.23 (4278 hom., cov: 33)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Benign reviewed by expert panel B:2
• Conservation: PhyloP100: -0.513
• 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 -10 ACMG points.

• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BP7: For more information check the summary or visit ClinGen Evidence Repository.
• BA1: For more information check the summary or visit ClinGen Evidence Repository.

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.508+232A>G		intron	N/A	NP_001745.2
	RUNX1	NM_001001890.3		c.427+232A>G		intron	N/A	NP_001001890.1	Q01196-1
	RUNX1	NM_001122607.2		c.427+232A>G		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.508+232A>G		intron	N/A	ENSP00000501943.1	Q01196-8
	RUNX1	ENST00000300305.7	TSL:1	c.508+232A>G		intron	N/A	ENSP00000300305.3	Q01196-8
	RUNX1	ENST00000344691.8	TSL:1	c.427+232A>G		intron	N/A	ENSP00000340690.4	Q01196-1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34445 AN: 152054 Hom.: 4273 Cov.: 33

Gnomad AFR AF: 0.305

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.227 AC: 34491 AN: 152172 Hom.: 4278 Cov.: 33 AF XY: 0.223 AC XY: 16597 AN XY: 74402

African (AFR) AF: 0.305 AC: 12668 AN: 41500

American (AMR) AF: 0.143 AC: 2188 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 608 AN: 3468

East Asian (EAS) AF: 0.0982 AC: 510 AN: 5192

South Asian (SAS) AF: 0.113 AC: 544 AN: 4832

European-Finnish (FIN) AF: 0.207 AC: 2195 AN: 10580

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.223 AC: 15133 AN: 67996

Other (OTH) AF: 0.197 AC: 417 AN: 2116

Alfa AF: 0.210 Hom.: 2640

Bravo AF: 0.224

Asia WGS AF: 0.118 AC: 411 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: reviewed by expert panel

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.30
PhyloP100		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2298352; hg19: chr21-36252622;