ENST00000338888.4:c.58+13023G>A

Variant names:

• chr1-24951491-C-T
• rs11249206
• ENST00000338888.4:c.58+13023G>A

Variant summary

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

The ENST00000338888.4(RUNX3):​c.58+13023G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 152,024 control chromosomes in the GnomAD database, including 18,505 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 (18505 hom., cov: 32)
• Consequence: RUNX3 ENST00000338888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_001031680.2	c.58+13023G>A		intron_variant	Intron 1 of 5		NP_001026850.1
RUNX3	NM_001320672.1	c.58+13023G>A		intron_variant	Intron 2 of 6		NP_001307601.1
RUNX3	XM_005246024.5	c.58+13023G>A		intron_variant	Intron 2 of 6		XP_005246081.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000338888.4	c.58+13023G>A		intron_variant	Intron 2 of 6	1		ENSP00000343477.3
RUNX3	ENST00000479341.1	n.168+13023G>A		intron_variant	Intron 2 of 2	1
RUNX3	ENST00000399916.5	c.58+13023G>A		intron_variant	Intron 1 of 5	2		ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73481 AN: 151906 Hom.: 18476 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.486

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

GnomAD4 genome AF: 0.484 AC: 73557 AN: 152024 Hom.: 18505 Cov.: 32 AF XY: 0.493 AC XY: 36621 AN XY: 74324

African (AFR) AF: 0.339 AC: 14032 AN: 41444

American (AMR) AF: 0.590 AC: 9027 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1587 AN: 3470

East Asian (EAS) AF: 0.648 AC: 3344 AN: 5160

South Asian (SAS) AF: 0.552 AC: 2657 AN: 4810

European-Finnish (FIN) AF: 0.611 AC: 6451 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34700 AN: 67970

Other (OTH) AF: 0.493 AC: 1043 AN: 2116

Alfa AF: 0.503 Hom.: 83870

Bravo AF: 0.475

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.74
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

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Other links and lift over

dbSNP: rs11249206; hg19: chr1-25277982;