1-24927826-C-T

Variant names:

• chr1-24927826-C-T
• rs7517302
• NM_004350.3:c.283-96G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004350.3(RUNX3):​c.283-96G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,062,078 control chromosomes in the GnomAD database, including 166,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (21523 hom., cov: 32)
  • Exomes 𝑓: 0.56 (145048 hom.)
• Consequence: RUNX3 NM_004350.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.67
• Publications: 23 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-24927826-C-T is Benign according to our data. Variant chr1-24927826-C-T is described in ClinVar as [Benign]. Clinvar id is 2688389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUNX3	NM_004350.3	c.283-96G>A		intron_variant	Intron 1 of 4	ENST00000308873.11	NP_004341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUNX3	ENST00000308873.11	c.283-96G>A		intron_variant	Intron 1 of 4	1	NM_004350.3	ENSP00000308051.6
RUNX3	ENST00000338888.4	c.325-96G>A		intron_variant	Intron 3 of 6	1		ENSP00000343477.3
RUNX3	ENST00000399916.5	c.325-96G>A		intron_variant	Intron 2 of 5	2		ENSP00000382800.1
RUNX3	ENST00000496967.1	n.57-96G>A		intron_variant	Intron 1 of 4	3

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80426 AN: 151894 Hom.: 21481 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.577

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.562 AC: 511551 AN: 910066 Hom.: 145048 AF XY: 0.562 AC XY: 262980 AN XY: 468180

African (AFR) AF: 0.457 AC: 10520 AN: 23002

American (AMR) AF: 0.631 AC: 26019 AN: 41226

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 10860 AN: 20652

East Asian (EAS) AF: 0.547 AC: 20100 AN: 36742

South Asian (SAS) AF: 0.574 AC: 40396 AN: 70400

European-Finnish (FIN) AF: 0.554 AC: 27540 AN: 49674

Middle Eastern (MID) AF: 0.491 AC: 2238 AN: 4558

European-Non Finnish (NFE) AF: 0.564 AC: 350786 AN: 622048

Other (OTH) AF: 0.553 AC: 23092 AN: 41764

GnomAD4 genome AF: 0.530 AC: 80523 AN: 152012 Hom.: 21523 Cov.: 32 AF XY: 0.528 AC XY: 39232 AN XY: 74282

African (AFR) AF: 0.458 AC: 18988 AN: 41462

American (AMR) AF: 0.558 AC: 8527 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1865 AN: 3468

East Asian (EAS) AF: 0.518 AC: 2681 AN: 5178

South Asian (SAS) AF: 0.576 AC: 2777 AN: 4818

European-Finnish (FIN) AF: 0.565 AC: 5962 AN: 10558

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37841 AN: 67940

Other (OTH) AF: 0.520 AC: 1094 AN: 2104

Alfa AF: 0.550 Hom.: 20554

Bravo AF: 0.534

Asia WGS AF: 0.505 AC: 1752 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 54. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.75
DANN	Benign	0.49
PhyloP100		-1.7
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: rs7517302; hg19: chr1-25254317; COSMIC: COSV58243002; COSMIC: COSV58243002;