rs11088302

Variant names:

• chr21-34991865-A-G
• rs11088302
• NM_001754.5:c.58+56977T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-34991865-A-G
• chr21-34991865-A-T

Variant summary

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

The NM_001754.5(RUNX1):​c.58+56977T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,088 control chromosomes in the GnomAD database, including 30,058 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 0.60 (30058 hom., cov: 32)
• Consequence: RUNX1 NM_001754.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 5 publications found

Genes affected

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]

RUNX1 Gene-Disease associations (from GenCC):

• hereditary thrombocytopenia and hematologic cancer predisposition syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae)
• acute myeloid leukemia

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.58+56977T>C		intron_variant	Intron 2 of 8	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.58+56977T>C		intron_variant	Intron 2 of 8		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91755 AN: 151970 Hom.: 30021 Cov.: 32

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.524

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.604 AC: 91844 AN: 152088 Hom.: 30058 Cov.: 32 AF XY: 0.597 AC XY: 44405 AN XY: 74324

African (AFR) AF: 0.876 AC: 36353 AN: 41516

American (AMR) AF: 0.540 AC: 8246 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2111 AN: 3472

East Asian (EAS) AF: 0.524 AC: 2693 AN: 5144

South Asian (SAS) AF: 0.542 AC: 2618 AN: 4826

European-Finnish (FIN) AF: 0.409 AC: 4323 AN: 10558

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33615 AN: 67974

Other (OTH) AF: 0.589 AC: 1243 AN: 2110

Alfa AF: 0.531 Hom.: 33307

Bravo AF: 0.623

Asia WGS AF: 0.603 AC: 2097 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.8
DANN	Benign	0.48
PhyloP100		0.18

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: rs11088302; hg19: chr21-36364162;