1-24913850-T-C

Variant names:

• chr1-24913850-T-C
• rs2236850
• NM_004350.3:c.544+5390A>G

Variant summary

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

The NM_004350.3(RUNX3):​c.544+5390A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,122 control chromosomes in the GnomAD database, including 26,774 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 0.56 (26774 hom., cov: 33)
• Consequence: RUNX3 NM_004350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0470
• Publications: 11 publications found

Genes affected

RUNX3 (HGNC:10473): (RUNX family transcription factor 3) This gene encodes a member of the runt domain-containing family of transcription factors. A heterodimer of this protein and a beta subunit forms a complex that binds to the core DNA sequence 5'-PYGPYGGT-3' found in a number of enhancers and promoters, and can either activate or suppress transcription. It also interacts with other transcription factors. It functions as a tumor suppressor, and the gene is frequently deleted or transcriptionally silenced in cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_004350.3	c.544+5390A>G		intron_variant	Intron 3 of 4	ENST00000308873.11	NP_004341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000308873.11	c.544+5390A>G		intron_variant	Intron 3 of 4	1	NM_004350.3	ENSP00000308051.6
RUNX3	ENST00000338888.4	c.586+5390A>G		intron_variant	Intron 5 of 6	1		ENSP00000343477.3
RUNX3	ENST00000399916.5	c.586+5390A>G		intron_variant	Intron 4 of 5	2		ENSP00000382800.1
RUNX3	ENST00000496967.1	n.318+5390A>G		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85533 AN: 152004 Hom.: 26744 Cov.: 33

Gnomad AFR AF: 0.860

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.563 AC: 85609 AN: 152122 Hom.: 26774 Cov.: 33 AF XY: 0.560 AC XY: 41646 AN XY: 74384

African (AFR) AF: 0.860 AC: 35718 AN: 41552

American (AMR) AF: 0.488 AC: 7469 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.499 AC: 1733 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1849 AN: 5174

South Asian (SAS) AF: 0.414 AC: 1995 AN: 4814

European-Finnish (FIN) AF: 0.460 AC: 4871 AN: 10586

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30296 AN: 67926

Other (OTH) AF: 0.547 AC: 1154 AN: 2108

Alfa AF: 0.475 Hom.: 24997

Bravo AF: 0.573

Asia WGS AF: 0.478 AC: 1665 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		0.047
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: rs2236850; hg19: chr1-25240341;