rs1555898635

Positions:

• chr21-34880663-A-G
• chr21-34880663-A-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. BP4 BP7 PM2_Supporting

This summary comes from the ClinGen Evidence Repository: This c.402T>C (p.Ala134=) synonymous variant is located at a non-conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP score = -2.40196 in GRCh38); it is not predicted to have any splicing impact per SpliceAI (BP7+BP4). The variant is absent from population databases, including gnomAD v2 and v3 (PM2_supporting). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1 (version 2): BP4, BP7, and PM2_supporting. LINK:https://erepo.genome.network/evrepo/ui/classification/CA512318752/MONDO:0011071/008

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUNX1 NM_001754.5 synonymous
• Clinical Significance: Likely benign reviewed by expert panel B:2
• Conservation: PhyloP100: -2.35

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]

LOC112267915 (HGNC:):

RUNX1-AS1 (HGNC:56821): (RUNX1 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• PM2: For more information check the summary or visit ClinGen Evidence Repository.
• BP4: For more information check the summary or visit ClinGen Evidence Repository.
• BP7: For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.402T>C	p.Ala134=	synonymous_variant	5/9	ENST00000675419.1	NP_001745.2
LOC112267915	XR_007067853.1	n.14431A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.402T>C	p.Ala134=	synonymous_variant	5/9		NM_001754.5	ENSP00000501943	A1
RUNX1-AS1	ENST00000651798.1	n.662-2820A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: reviewed by expert panel

Submissions by phenotype

Hereditary thrombocytopenia and hematologic cancer predisposition syndrome Benign:1

Likely benign, reviewed by expert panel

curation

ClinGen Myeloid Malignancy Variant Curation Expert Panel

Jul 07, 2022

This c.402T>C (p.Ala134=) synonymous variant is located at a non-conserved nucleotide per an evolutionary conservation prediction algorithm (PhyloP score = -2.40196 in GRCh38); it is not predicted to have any splicing impact per SpliceAI (BP7+BP4). The variant is absent from population databases, including gnomAD v2 and v3 (PM2_supporting). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the ClinGen Myeloid Malignancy Variant Curation Expert Panel for RUNX1 (version 2): BP4, BP7, and PM2_supporting. -

Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 04, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.52

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: rs1555898635; hg19: chr21-36252960;