Variant 8-91986880-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000523629.7(RUNX1T1):c.1077+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,546,428 control chromosomes in the GnomAD database, including 257 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 130 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 127 hom. )

Consequence

RUNX1T1
ENST00000523629.7 splice_region, intron

Scores

Splicing: ADA: 0.0009971

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0150

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 8-91986880-G-A is Benign according to our data. Variant chr8-91986880-G-A is described in ClinVar as [Benign]. Clinvar id is 784134.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1T1	NM_175634.3 linkuse as main transcript	c.1077+7C>T		splice_region_variant, intron_variant		ENST00000523629.7	NP_783552.1
RUNX1T1	XR_007060758.1 linkuse as main transcript	n.1420+7C>T		splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1T1	ENST00000523629.7 linkuse as main transcript	c.1077+7C>T		splice_region_variant, intron_variant		5	NM_175634.3	ENSP00000428543		Q06455-1

Frequencies

GnomAD3 genomes

AF:

0.0230

AC:

3500

AN:

151876

Hom.:

126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0799

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00755

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.00623

AC:

1561

AN:

250702

Hom.:

AF XY:

0.00458

AC XY:

621

AN XY:

135542

show subpopulations

Gnomad AFR exome

AF:

0.0807

Gnomad AMR exome

AF:

0.00437

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000476

Gnomad OTH exome

AF:

0.00425

GnomAD4 exome

AF:

0.00264

AC:

3678

AN:

1394436

Hom.:

127

Cov.:

AF XY:

0.00239

AC XY:

1669

AN XY:

698196

show subpopulations

Gnomad4 AFR exome

AF:

0.0830

Gnomad4 AMR exome

AF:

0.00470

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.000577

Gnomad4 FIN exome

AF:

0.0000379

Gnomad4 NFE exome

AF:

0.000371

Gnomad4 OTH exome

AF:

0.00564

GnomAD4 genome

AF:

0.0233

AC:

3534

AN:

151992

Hom.:

130

Cov.:

AF XY:

0.0225

AC XY:

1671

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.00754

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000530

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0262

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

RUNX1T1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.3

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0010

dbscSNV1_RF

Benign

0.072

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over