ENST00000523629.6:c.-86+10280C>T

Variant names:

• chr8-92092577-G-A
• rs1552314
• NM_175634.3:c.-86+10280C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000523629.7(RUNX1T1):​c.-86+10280C>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 ENST00000523629.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.784
• Publications: 5 publications found

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]

RUNX1T1 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000523629.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1T1	NM_175634.3	MANE Select	c.-86+10280C>T		intron	N/A	NP_783552.1	Q06455-1
	RUNX1T1	NM_001198679.3		c.265+2451C>T		intron	N/A	NP_001185608.1	A0A0A0MSU1
	RUNX1T1	NM_001395209.1		c.172+2451C>T		intron	N/A	NP_001382138.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1T1	ENST00000523629.7	TSL:5 MANE Select	c.-86+10280C>T		intron	N/A	ENSP00000428543.1	Q06455-1
	RUNX1T1	ENST00000518844.5	TSL:1	c.-309+2451C>T		intron	N/A	ENSP00000430728.1	Q06455-2
	RUNX1T1	ENST00000360348.6	TSL:1	c.-24+2451C>T		intron	N/A	ENSP00000353504.2	Q06455-4

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

African (AFR) AF: 0.227 AC: 9411 AN: 41486

American (AMR) AF: 0.755 AC: 11539 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2647 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5140 AN: 5178

South Asian (SAS) AF: 0.832 AC: 4017 AN: 4828

European-Finnish (FIN) AF: 0.814 AC: 8621 AN: 10594

Middle Eastern (MID) AF: 0.668 AC: 195 AN: 292

European-Non Finnish (NFE) AF: 0.783 AC: 53194 AN: 67978

Other (OTH) AF: 0.667 AC: 1412 AN: 2116

Alfa AF: 0.728 Hom.: 55113

Bravo AF: 0.612

Asia WGS AF: 0.867 AC: 3005 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.70
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1552314; hg19: chr8-93104805;