NM_175634.3:c.89-7204A>G

Variant names:

• chr8-92024567-T-C
• rs9297901
• NM_175634.3:c.89-7204A>G

Variant summary

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

The NM_175634.3(RUNX1T1):​c.89-7204A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 147,294 control chromosomes in the GnomAD database, including 4,882 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 0.24 (4882 hom., cov: 28)
• Consequence: RUNX1T1 NM_175634.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 1 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_175634.3. 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.89-7204A>G		intron	N/A	NP_783552.1	Q06455-1
	RUNX1T1	NM_001198679.3		c.266-7204A>G		intron	N/A	NP_001185608.1	A0A0A0MSU1
	RUNX1T1	NM_001395209.1		c.173-7204A>G		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.89-7204A>G		intron	N/A	ENSP00000428543.1	Q06455-1
	RUNX1T1	ENST00000396218.5	TSL:1	c.8-7204A>G		intron	N/A	ENSP00000379520.1	Q06455-2
	RUNX1T1	ENST00000518844.5	TSL:1	c.8-7204A>G		intron	N/A	ENSP00000430728.1	Q06455-2

Frequencies

GnomAD3 genomes AF: 0.245 AC: 36019 AN: 147206 Hom.: 4863 Cov.: 28

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.289

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.245 AC: 36077 AN: 147294 Hom.: 4882 Cov.: 28 AF XY: 0.239 AC XY: 17150 AN XY: 71622

African (AFR) AF: 0.362 AC: 14308 AN: 39554

American (AMR) AF: 0.197 AC: 2903 AN: 14712

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 763 AN: 3440

East Asian (EAS) AF: 0.00773 AC: 39 AN: 5044

South Asian (SAS) AF: 0.165 AC: 764 AN: 4628

European-Finnish (FIN) AF: 0.177 AC: 1686 AN: 9534

Middle Eastern (MID) AF: 0.287 AC: 81 AN: 282

European-Non Finnish (NFE) AF: 0.222 AC: 14880 AN: 67174

Other (OTH) AF: 0.231 AC: 469 AN: 2026

Alfa AF: 0.230 Hom.: 1663

Bravo AF: 0.257

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.15
DANN	Benign	0.46
PhyloP100		-1.5
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: rs9297901; hg19: chr8-93036795;