20-43709235-C-G

Variant names:

• chr20-43709235-C-G
• rs285171
• NM_002466.4:c.1506-728C>G

Variant summary

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

The ENST00000217026.5(MYBL2):​c.1506-728C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,024 control chromosomes in the GnomAD database, including 44,272 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 0.75 (44272 hom., cov: 31)
• Consequence: MYBL2 ENST00000217026.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 8 publications found

Genes affected

MYBL2 (HGNC:7548): (MYB proto-oncogene like 2) The protein encoded by this gene, a member of the MYB family of transcription factor genes, is a nuclear protein involved in cell cycle progression. The encoded protein is phosphorylated by cyclin A/cyclin-dependent kinase 2 during the S-phase of the cell cycle and possesses both activator and repressor activities. It has been shown to activate the cell division cycle 2, cyclin D1, and insulin-like growth factor-binding protein 5 genes. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000217026.5. 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
	MYBL2	NM_002466.4	MANE Select	c.1506-728C>G		intron	N/A	NP_002457.1
	MYBL2	NM_001278610.2		c.1434-728C>G		intron	N/A	NP_001265539.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYBL2	ENST00000217026.5	TSL:1 MANE Select	c.1506-728C>G		intron	N/A	ENSP00000217026.4
	MYBL2	ENST00000396863.8	TSL:2	c.1434-728C>G		intron	N/A	ENSP00000380072.4

Frequencies

GnomAD3 genomes AF: 0.755 AC: 114631 AN: 151906 Hom.: 44251 Cov.: 31

Gnomad AFR AF: 0.580

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.777

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.752

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.750

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

GnomAD4 genome AF: 0.754 AC: 114688 AN: 152024 Hom.: 44272 Cov.: 31 AF XY: 0.758 AC XY: 56349 AN XY: 74304

African (AFR) AF: 0.580 AC: 24038 AN: 41444

American (AMR) AF: 0.754 AC: 11532 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 2694 AN: 3466

East Asian (EAS) AF: 0.803 AC: 4123 AN: 5136

South Asian (SAS) AF: 0.806 AC: 3885 AN: 4822

European-Finnish (FIN) AF: 0.856 AC: 9069 AN: 10592

Middle Eastern (MID) AF: 0.764 AC: 223 AN: 292

European-Non Finnish (NFE) AF: 0.835 AC: 56766 AN: 67964

Other (OTH) AF: 0.751 AC: 1583 AN: 2108

Alfa AF: 0.755 Hom.: 2780

Bravo AF: 0.736

Asia WGS AF: 0.773 AC: 2685 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.34
PhyloP100		-0.094
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: rs285171; hg19: chr20-42337875;