rs1395621

Variant names:

• chr1-24944081-T-C
• rs1395621
• ENST00000338888.4:c.59-14229A>G

Variant summary

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

The ENST00000338888.4(RUNX3):​c.59-14229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,972 control chromosomes in the GnomAD database, including 33,231 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 (33231 hom., cov: 31)
• Consequence: RUNX3 ENST00000338888.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586
• Publications: 13 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=-0.87).
• 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.59-14229A>G		intron_variant	Intron 1 of 5		NP_001026850.1
RUNX3	NM_001320672.1	c.59-14229A>G		intron_variant	Intron 2 of 6		NP_001307601.1
RUNX3-AS1	NR_183339.1	n.1730+5180T>C		intron_variant	Intron 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000338888.4	c.59-14229A>G		intron_variant	Intron 2 of 6	1		ENSP00000343477.3
RUNX3	ENST00000479341.1	n.169-14229A>G		intron_variant	Intron 2 of 2	1
RUNX3	ENST00000399916.5	c.59-14229A>G		intron_variant	Intron 1 of 5	2		ENSP00000382800.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96596 AN: 151854 Hom.: 33160 Cov.: 31

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.636 AC: 96729 AN: 151972 Hom.: 33231 Cov.: 31 AF XY: 0.641 AC XY: 47645 AN XY: 74272

African (AFR) AF: 0.904 AC: 37455 AN: 41454

American (AMR) AF: 0.641 AC: 9811 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1777 AN: 3470

East Asian (EAS) AF: 0.581 AC: 2995 AN: 5156

South Asian (SAS) AF: 0.755 AC: 3626 AN: 4802

European-Finnish (FIN) AF: 0.545 AC: 5741 AN: 10540

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33531 AN: 67936

Other (OTH) AF: 0.599 AC: 1262 AN: 2108

Alfa AF: 0.543 Hom.: 11932

Bravo AF: 0.647

Asia WGS AF: 0.729 AC: 2536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.26
DANN	Benign	0.38
PhyloP100		-0.59
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: rs1395621; hg19: chr1-25270572;