21-34792182-T-G

Variant names:

• chr21-34792182-T-G
• NM_001754.5:c.1396A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001754.5(RUNX1):​c.1396A>C​(p.Met466Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000058 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RUNX1 NM_001754.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18520218).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX1	NM_001754.5	c.1396A>C	p.Met466Leu	missense_variant	Exon 9 of 9	ENST00000675419.1	NP_001745.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX1	ENST00000675419.1	c.1396A>C	p.Met466Leu	missense_variant	Exon 9 of 9		NM_001754.5	ENSP00000501943.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1 AN: 151092 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000968

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000580 AC: 8 AN: 1378702 Hom.: 0 Cov.: 32 AF XY: 0.00000441 AC XY: 3 AN XY: 680900

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000409

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000464

Gnomad4 OTH exome AF: 0.0000349

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000661 AC: 1 AN: 151214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 73914

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000968

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Benign	0.88
DEOGEN2	Benign	0.30	T;.;.;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.88	D;D;.;D
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.86	L;.;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.42	N;N;N;N
REVEL	Benign	0.15
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.70	P;P;P;.
Vest4		0.19
MutPred		0.62		Loss of catalytic residue at M439 (P = 0.0082);.;.;.;
MVP		0.39
MPC		1.5
ClinPred		0.72	D
GERP RS		4.7
Varity_R		0.46
gMVP		0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-36164479;