rs990074

Positions:

• chr21-35538855-T-C
• chr21-35538855-T-G
• chr21-35538855-T-A

Variant summary

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

The NR_073512.1(LOC100506403):​n.105+41805A>G 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 0.669 in 152,132 control chromosomes in the GnomAD database, including 34,892 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 0.67 (34892 hom., cov: 33)
• Consequence: LOC100506403 NR_073512.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211

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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC100506403	NR_073512.1	n.105+41805A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000475045.6	c.-262+41805A>G		intron_variant		5
RUNX1	ENST00000467692.5	n.101+41805A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.669 AC: 101767 AN: 152014 Hom.: 34858 Cov.: 33

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.612

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.657

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

GnomAD4 genome AF: 0.669 AC: 101850 AN: 152132 Hom.: 34892 Cov.: 33 AF XY: 0.671 AC XY: 49885 AN XY: 74350

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.633

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.826

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.612

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.656

Alfa AF: 0.634 Hom.: 6571

Bravo AF: 0.679

Asia WGS AF: 0.787 AC: 2739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs990074; hg19: chr21-36911152;