rs760805

Variant names:

• chr1-24925432-A-T
• rs760805
• NM_004350.3:c.439+2142T>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.439+2142T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,712 control chromosomes in the GnomAD database, including 16,743 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 0.43 (16743 hom., cov: 29)
• Consequence: RUNX3 NM_004350.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 27 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=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_004350.3	c.439+2142T>A		intron_variant	Intron 2 of 4	ENST00000308873.11	NP_004341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000308873.11	c.439+2142T>A		intron_variant	Intron 2 of 4	1	NM_004350.3	ENSP00000308051.6
RUNX3	ENST00000338888.4	c.481+2142T>A		intron_variant	Intron 4 of 6	1		ENSP00000343477.3
RUNX3	ENST00000399916.5	c.481+2142T>A		intron_variant	Intron 3 of 5	2		ENSP00000382800.1
RUNX3	ENST00000496967.1	n.213+2142T>A		intron_variant	Intron 2 of 4	3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64685 AN: 151594 Hom.: 16735 Cov.: 29

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.454

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

GnomAD4 genome AF: 0.426 AC: 64693 AN: 151712 Hom.: 16743 Cov.: 29 AF XY: 0.428 AC XY: 31734 AN XY: 74124

African (AFR) AF: 0.112 AC: 4620 AN: 41358

American (AMR) AF: 0.514 AC: 7834 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1790 AN: 3472

East Asian (EAS) AF: 0.511 AC: 2627 AN: 5140

South Asian (SAS) AF: 0.570 AC: 2740 AN: 4806

European-Finnish (FIN) AF: 0.560 AC: 5875 AN: 10482

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.552 AC: 37495 AN: 67888

Other (OTH) AF: 0.449 AC: 946 AN: 2106

Alfa AF: 0.472 Hom.: 2342

Bravo AF: 0.415

Asia WGS AF: 0.472 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.85
PhyloP100		1.4
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: rs760805; hg19: chr1-25251923;