1-24917063-C-T

Variant names:

• chr1-24917063-C-T
• rs2236851
• NM_004350.3:c.544+2177G>A

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+2177G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,218 control chromosomes in the GnomAD database, including 1,531 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 0.12 (1531 hom., cov: 32)
• Consequence: RUNX3 NM_004350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.522
• Publications: 8 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_004350.3	c.544+2177G>A		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+2177G>A		intron_variant	Intron 3 of 4	1	NM_004350.3	ENSP00000308051.6
RUNX3	ENST00000338888.4	c.586+2177G>A		intron_variant	Intron 5 of 6	1		ENSP00000343477.3
RUNX3	ENST00000399916.5	c.586+2177G>A		intron_variant	Intron 4 of 5	2		ENSP00000382800.1
RUNX3	ENST00000496967.1	n.318+2177G>A		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19025 AN: 152100 Hom.: 1530 Cov.: 32

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0968

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.125 AC: 19023 AN: 152218 Hom.: 1531 Cov.: 32 AF XY: 0.124 AC XY: 9241 AN XY: 74434

African (AFR) AF: 0.0305 AC: 1266 AN: 41556

American (AMR) AF: 0.0966 AC: 1478 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 531 AN: 3470

East Asian (EAS) AF: 0.130 AC: 671 AN: 5170

South Asian (SAS) AF: 0.128 AC: 618 AN: 4822

European-Finnish (FIN) AF: 0.167 AC: 1767 AN: 10600

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12331 AN: 67982

Other (OTH) AF: 0.118 AC: 248 AN: 2110

Alfa AF: 0.156 Hom.: 2212

Bravo AF: 0.115

Asia WGS AF: 0.109 AC: 378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		-0.52
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: rs2236851; hg19: chr1-25243554;