rs2248720

Positions:

• chr21-34859859-C-A
• chr21-34859859-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4 BP2 BA1 BP7

This summary comes from the ClinGen Evidence Repository: NM_001754.5(RUNX1):c.509-281G>T is an intronic variant which has a MAF of 0.8530 (85.3%, 35321/41406, 35321 alleles) in the African/African American subpopulation of the gnomAD 3.1.2 cohort which is ≥ 0.0015 (0.15%) (BA1). This variant is detected in a homozygous state in 15115 individuals in a population database (gnomAD 3.1.2) (BP2). This intronic variant has a SpliceAI score ≤ 0.20 (0.0) (BP4). This variant has a SpliceAI score ≤ 0.20 (0.0) and evolutionary conservation prediction algorithms predict the site as not being conserved (PhyloP score ≤ 2.0 (-0.45) (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, BP2, BP4, BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA15984361/MONDO:0011071/008

• Frequency: Genomes: 𝑓 0.58 (28231 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.439

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP2: For more information check the summary or visit ClinGen Evidence Repository.
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.509-281G>T		intron_variant		ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.509-281G>T		intron_variant			NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87737 AN: 151974 Hom.: 28198 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.456

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.518

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.577 AC: 87816 AN: 152092 Hom.: 28231 Cov.: 32 AF XY: 0.563 AC XY: 41864 AN XY: 74340

Gnomad4 AFR AF: 0.853

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.518

Gnomad4 OTH AF: 0.563

Alfa AF: 0.515 Hom.: 10642

Bravo AF: 0.585

Asia WGS AF: 0.314 AC: 1098 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.31

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

Publications

LitVar

Other links and lift over

dbSNP: rs2248720; hg19: chr21-36232156;