1-24946709-T-C

Variant names:

• chr1-24946709-T-C
• rs7551188
• ENST00000338888.4:c.59-16857A>G

Variant summary

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

The ENST00000338888.4(RUNX3):​c.59-16857A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,826 control chromosomes in the GnomAD database, including 17,481 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 0.48 (17481 hom., cov: 30)
• Consequence: RUNX3 ENST00000338888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 18 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]

RUNX3-AS1 (HGNC:40513): (RUNX3 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_001031680.2	c.59-16857A>G		intron_variant	Intron 1 of 5		NP_001026850.1
RUNX3	NM_001320672.1	c.59-16857A>G		intron_variant	Intron 2 of 6		NP_001307601.1
RUNX3-AS1	NR_183339.1	n.1730+7808T>C		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000338888.4	c.59-16857A>G		intron_variant	Intron 2 of 6	1		ENSP00000343477.3
RUNX3	ENST00000479341.1	n.169-16857A>G		intron_variant	Intron 2 of 2	1
RUNX3	ENST00000399916.5	c.59-16857A>G		intron_variant	Intron 1 of 5	2		ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72585 AN: 151708 Hom.: 17454 Cov.: 30

Gnomad AFR AF: 0.433

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.479 AC: 72657 AN: 151826 Hom.: 17481 Cov.: 30 AF XY: 0.485 AC XY: 35999 AN XY: 74200

African (AFR) AF: 0.433 AC: 17908 AN: 41366

American (AMR) AF: 0.547 AC: 8365 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.397 AC: 1377 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2698 AN: 5148

South Asian (SAS) AF: 0.540 AC: 2596 AN: 4806

European-Finnish (FIN) AF: 0.542 AC: 5714 AN: 10534

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32356 AN: 67904

Other (OTH) AF: 0.474 AC: 1000 AN: 2108

Alfa AF: 0.473 Hom.: 51257

Bravo AF: 0.471

Asia WGS AF: 0.580 AC: 2019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.30
DANN	Benign	0.33
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7551188; hg19: chr1-25273200; COSMIC: COSV58846165;