rs8133843

chr21-35365944-G-Achr21-35365944-G-Cchr21-35365944-G-T

Variant summary

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

The ENST00000475045.6(RUNX1):c.-197+96017C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 151,988 control chromosomes in the GnomAD database, including 31,798 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 0.65 (31798 hom., cov: 33)
• Consequence: RUNX1 ENST00000475045.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.704 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.-197+96017C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.645 AC: 97986 AN: 151870 Hom.: 31759 Cov.: 33

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.651

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.645 AC: 98088 AN: 151988 Hom.: 31798 Cov.: 33 AF XY: 0.646 AC XY: 47960 AN XY: 74254

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.635

Gnomad4 FIN AF: 0.651

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.624

Alfa AF: 0.641 Hom.: 3857

Bravo AF: 0.647

Asia WGS AF: 0.575 AC: 1991 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.10
Dann	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8133843; hg19: chr21-36738242;