rs2300395

Positions:

• chr21-34872901-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001754.5(RUNX1):​c.508+7656G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 152,002 control chromosomes in the GnomAD database, including 18,808 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 0.43 (18808 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806

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]

LOC112267915 (HGNC:):

RUNX1-AS1 (HGNC:56821): (RUNX1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.508+7656G>A		intron_variant		ENST00000675419.1	NP_001745.2
LOC112267915	XR_007067853.1	n.6669C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.508+7656G>A		intron_variant			NM_001754.5	ENSP00000501943	A1
RUNX1-AS1	ENST00000651798.1	n.662-10582C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65384 AN: 151882 Hom.: 18752 Cov.: 32

Gnomad AFR AF: 0.826

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.431 AC: 65503 AN: 152002 Hom.: 18808 Cov.: 32 AF XY: 0.423 AC XY: 31420 AN XY: 74276

Gnomad4 AFR AF: 0.826

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.297

Gnomad4 OTH AF: 0.376

Alfa AF: 0.301 Hom.: 16461

Bravo AF: 0.445

Asia WGS AF: 0.268 AC: 933 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.26
DANN	Benign	0.44

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: rs2300395; hg19: chr21-36245198;