rs7279383

Variant names:

• chr21-34852666-C-G
• rs7279383
• NM_001754.5:c.613+6808G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-34852666-C-G
• chr21-34852666-C-T

Variant summary

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

The ENST00000675419.1(RUNX1):​c.613+6808G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,152 control chromosomes in the GnomAD database, including 1,954 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 0.16 (1954 hom., cov: 32)
• Consequence: RUNX1 ENST00000675419.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756
• Publications: 2 publications found

Genes affected

RUNX1 (HGNC:10471): (RUNX family transcription factor 1) Core binding factor (CBF) is a heterodimeric transcription factor that binds to the core element of many enhancers and promoters. The protein encoded by this gene represents the alpha subunit of CBF and is thought to be involved in the development of normal hematopoiesis. Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

RUNX1-AS1 (HGNC:56821): (RUNX1 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 (NFE) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000675419.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	NM_001754.5	MANE Select	c.613+6808G>C		intron	N/A	NP_001745.2
	RUNX1	NM_001001890.3		c.532+6808G>C		intron	N/A	NP_001001890.1
	RUNX1	NM_001122607.2		c.532+6808G>C		intron	N/A	NP_001116079.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUNX1	ENST00000675419.1	MANE Select	c.613+6808G>C		intron	N/A	ENSP00000501943.1
	RUNX1	ENST00000300305.7	TSL:1	c.613+6808G>C		intron	N/A	ENSP00000300305.3
	RUNX1	ENST00000344691.8	TSL:1	c.532+6808G>C		intron	N/A	ENSP00000340690.4

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23592 AN: 152034 Hom.: 1953 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0122

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0996

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.155 AC: 23608 AN: 152152 Hom.: 1954 Cov.: 32 AF XY: 0.152 AC XY: 11324 AN XY: 74374

African (AFR) AF: 0.137 AC: 5691 AN: 41508

American (AMR) AF: 0.151 AC: 2313 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3470

East Asian (EAS) AF: 0.0122 AC: 63 AN: 5158

South Asian (SAS) AF: 0.169 AC: 817 AN: 4830

European-Finnish (FIN) AF: 0.0996 AC: 1054 AN: 10580

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12372 AN: 68000

Other (OTH) AF: 0.172 AC: 362 AN: 2110

Alfa AF: 0.0599 Hom.: 63

Bravo AF: 0.155

Asia WGS AF: 0.0820 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.34
PhyloP100		-0.76

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: rs7279383; hg19: chr21-36224963;