rs9976122

Positions:

• chr21-34966009-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.59-73046G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,230 control chromosomes in the GnomAD database, including 942 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 0.090 (942 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUNX1	NM_001754.5	c.59-73046G>A		intron_variant		ENST00000675419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000675419.1	c.59-73046G>A		intron_variant			NM_001754.5	A1

Frequencies

GnomAD3 genomes AF: 0.0903 AC: 13733 AN: 152112 Hom.: 936 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0646

Gnomad EAS AF: 0.0526

Gnomad SAS AF: 0.0395

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0924

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

GnomAD4 genome AF: 0.0903 AC: 13752 AN: 152230 Hom.: 942 Cov.: 32 AF XY: 0.0902 AC XY: 6716 AN XY: 74430

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0646

Gnomad4 EAS AF: 0.0527

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.0672

Gnomad4 NFE AF: 0.0437

Gnomad4 OTH AF: 0.0915

Alfa AF: 0.0558 Hom.: 158

Bravo AF: 0.0990

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.086
DANN	Benign	0.64

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: rs9976122; hg19: chr21-36338306;