rs2835189

chr21-35969823-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_110418.1(LOC101928269):n.664+252A>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,194 control chromosomes in the GnomAD database, including 1,199 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 0.11 (1199 hom., cov: 32)
• Consequence: LOC101928269 NR_110418.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0980

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]

LOC101928269 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC101928269	NR_110418.1	n.664+252A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUNX1	ENST00000460207.1	n.437+252A>C		intron_variant, non_coding_transcript_variant		1
RUNX1	ENST00000475045.6	c.-771+252A>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17064 AN: 152076 Hom.: 1196 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.0860

Gnomad EAS AF: 0.0713

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.111

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

GnomAD4 genome AF: 0.112 AC: 17079 AN: 152194 Hom.: 1199 Cov.: 32 AF XY: 0.114 AC XY: 8462 AN XY: 74402

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.0860

Gnomad4 EAS AF: 0.0708

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.113

Alfa AF: 0.132 Hom.: 1878

Bravo AF: 0.105

Asia WGS AF: 0.179 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	6.1
Dann	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2835189; hg19: chr21-37342121;