rs2835104

chr21-35718977-A-G

Variant summary

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

The ENST00000412240.1(ENSG00000230794):n.41-5530T>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 0.616 in 152,118 control chromosomes in the GnomAD database, including 30,333 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 0.62 (30333 hom., cov: 32)
• Consequence: ENST00000412240.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.83 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000412240.1	n.41-5530T>C		intron_variant, non_coding_transcript_variant		3
RUNX1	ENST00000475045.6	c.-587-64102T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93536 AN: 152000 Hom.: 30281 Cov.: 32

Gnomad AFR AF: 0.838

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.597

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.520

Gnomad OTH AF: 0.615

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

GnomAD4 genome AF: 0.616 AC: 93647 AN: 152118 Hom.: 30333 Cov.: 32 AF XY: 0.614 AC XY: 45677 AN XY: 74362

Gnomad4 AFR AF: 0.838

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.619

Alfa AF: 0.568 Hom.: 4341

Bravo AF: 0.633

Asia WGS AF: 0.501 AC: 1743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.3
Dann	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2835104; hg19: chr21-37091275;