ENST00000338888.4:c.59-11579A>G

Variant names:

• chr1-24941431-T-C
• rs4649038
• ENST00000338888.4:c.59-11579A>G

Variant summary

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

The ENST00000338888.4(RUNX3):​c.59-11579A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 152,112 control chromosomes in the GnomAD database, including 33,354 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 0.64 (33354 hom., cov: 32)
• Consequence: RUNX3 ENST00000338888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_001031680.2	c.59-11579A>G		intron_variant	Intron 1 of 5		NP_001026850.1
RUNX3	NM_001320672.1	c.59-11579A>G		intron_variant	Intron 2 of 6		NP_001307601.1
RUNX3-AS1	NR_183339.1	n.1730+2530T>C		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000338888.4	c.59-11579A>G		intron_variant	Intron 2 of 6	1		ENSP00000343477.3
RUNX3	ENST00000479341.1	n.169-11579A>G		intron_variant	Intron 2 of 2	1
RUNX3	ENST00000399916.5	c.59-11579A>G		intron_variant	Intron 1 of 5	2		ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96884 AN: 151994 Hom.: 33280 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.758

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.595

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

GnomAD4 genome AF: 0.638 AC: 97020 AN: 152112 Hom.: 33354 Cov.: 32 AF XY: 0.643 AC XY: 47791 AN XY: 74338

African (AFR) AF: 0.904 AC: 37520 AN: 41524

American (AMR) AF: 0.642 AC: 9810 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3470

East Asian (EAS) AF: 0.585 AC: 3027 AN: 5178

South Asian (SAS) AF: 0.757 AC: 3654 AN: 4824

European-Finnish (FIN) AF: 0.548 AC: 5792 AN: 10560

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33630 AN: 67968

Other (OTH) AF: 0.601 AC: 1265 AN: 2106

Alfa AF: 0.541 Hom.: 32987

Bravo AF: 0.648

Asia WGS AF: 0.741 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.23
PhyloP100		-2.0
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: rs4649038; hg19: chr1-25267922;