rs2247614

Positions:

• chr21-35259389-G-C
• chr21-35259389-G-T

Variant summary

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

The ENST00000475045.6(RUNX1):​c.-196-194317C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,210 control chromosomes in the GnomAD database, including 1,600 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 0.14 (1600 hom., cov: 32)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000475045.6	c.-196-194317C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21087 AN: 152090 Hom.: 1600 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.139 AC: 21105 AN: 152210 Hom.: 1600 Cov.: 32 AF XY: 0.138 AC XY: 10242 AN XY: 74432

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0980

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.157

Alfa AF: 0.0632 Hom.: 64

Bravo AF: 0.146

Asia WGS AF: 0.187 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.73
DANN	Benign	0.36

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2247614; hg19: chr21-36631687;