rs2834970

Positions:

• chr21-35553262-A-G
• chr21-35553262-A-T

Variant summary

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

The NR_073512.1(LOC100506403):​n.105+27398T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 152,022 control chromosomes in the GnomAD database, including 29,839 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 0.62 (29839 hom., cov: 32)
• Consequence: LOC100506403 NR_073512.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

Genes affected

LOC100506403 (HGNC:):

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC100506403	NR_073512.1	n.105+27398T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000475045.6	c.-262+27398T>C		intron_variant		5
RUNX1	ENST00000467692.5	n.101+27398T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94831 AN: 151904 Hom.: 29823 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.605

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.609

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

GnomAD4 genome AF: 0.624 AC: 94886 AN: 152022 Hom.: 29839 Cov.: 32 AF XY: 0.627 AC XY: 46610 AN XY: 74298

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.610

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.605

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.609

Alfa AF: 0.615 Hom.: 4561

Bravo AF: 0.628

Asia WGS AF: 0.768 AC: 2674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.7
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2834970; hg19: chr21-36925560;