rs933131

Variant names:

• chr21-34987391-G-A
• rs933131
• NM_001754.5:c.58+61451C>T

Variant summary

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

The NM_001754.5(RUNX1):​c.58+61451C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 151,976 control chromosomes in the GnomAD database, including 16,040 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 0.45 (16040 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.58+61451C>T		intron_variant	Intron 2 of 8	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.58+61451C>T		intron_variant	Intron 2 of 8		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68883 AN: 151858 Hom.: 16029 Cov.: 32

Gnomad AFR AF: 0.355

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.480

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.452

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

GnomAD4 genome AF: 0.454 AC: 68927 AN: 151976 Hom.: 16040 Cov.: 32 AF XY: 0.458 AC XY: 33990 AN XY: 74254

Gnomad4 AFR AF: 0.355

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.476

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.450

Alfa AF: 0.444 Hom.: 2152

Bravo AF: 0.442

Asia WGS AF: 0.432 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.082
DANN	Benign	0.79

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: rs933131; hg19: chr21-36359688;