chr21-34937166-T-C

Position:

• chr21-34937166-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001754.5(RUNX1):​c.59-44203A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,270 control chromosomes in the GnomAD database, including 82 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 0.024 (82 hom., cov: 31)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0237 (3606/152270) while in subpopulation NFE AF= 0.0382 (2598/68016). AF 95% confidence interval is 0.037. There are 82 homozygotes in gnomad4. There are 1672 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3606 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.59-44203A>G		intron_variant		ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.59-44203A>G		intron_variant			NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3605 AN: 152152 Hom.: 81 Cov.: 31

Gnomad AFR AF: 0.00601

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0317

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0382

Gnomad OTH AF: 0.0306

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

GnomAD4 genome AF: 0.0237 AC: 3606 AN: 152270 Hom.: 82 Cov.: 31 AF XY: 0.0225 AC XY: 1672 AN XY: 74454

Gnomad4 AFR AF: 0.00602

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0382

Gnomad4 OTH AF: 0.0307

Alfa AF: 0.0367 Hom.: 152

Bravo AF: 0.0238

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Benign	0.86

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: rs2834680; hg19: chr21-36309463;