rs1552314

Positions:

• chr8-92092577-G-A

Variant summary

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

The NM_001198679.3(RUNX1T1):​c.265+2451C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,140 control chromosomes in the GnomAD database, including 35,902 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 0.64 (35902 hom., cov: 34)
• Consequence: RUNX1T1 NM_001198679.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784

Genes affected

RUNX1T1 (HGNC:1535): (RUNX1 partner transcriptional co-repressor 1) This gene encodes a member of the myeloid translocation gene family which interact with DNA-bound transcription factors and recruit a range of corepressors to facilitate transcriptional repression. The t(8;21)(q22;q22) translocation is one of the most frequent karyotypic abnormalities in acute myeloid leukemia. The translocation produces a chimeric gene made up of the 5'-region of the runt-related transcription factor 1 gene fused to the 3'-region of this gene. The chimeric protein is thought to associate with the nuclear corepressor/histone deacetylase complex to block hematopoietic differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1T1	NM_001198679.3	c.265+2451C>T		intron_variant			NP_001185608.1
RUNX1T1	NM_001395209.1	c.172+2451C>T		intron_variant			NP_001382138.1
RUNX1T1	NM_001198634.2	c.121+2770C>T		intron_variant			NP_001185563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1T1	ENST00000523629.6	c.-86+10280C>T		intron_variant		5		ENSP00000428543.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96903 AN: 152022 Hom.: 35897 Cov.: 34

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.669

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.663

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

GnomAD4 genome AF: 0.637 AC: 96914 AN: 152140 Hom.: 35902 Cov.: 34 AF XY: 0.646 AC XY: 48070 AN XY: 74396

Gnomad4 AFR AF: 0.227

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.832

Gnomad4 FIN AF: 0.814

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.667

Alfa AF: 0.749 Hom.: 43820

Bravo AF: 0.612

Asia WGS AF: 0.867 AC: 3005 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.70

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: rs1552314; hg19: chr8-93104805;