20-32786714-A-G

Position:

• chr20-32786714-A-G

Variant summary

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

The NM_006892.4(DNMT3B):​c.432+87A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 1,594,342 control chromosomes in the GnomAD database, including 222,386 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 0.61 (31781 hom., cov: 33)
  • Exomes 𝑓: 0.50 (190605 hom.)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

Genes affected

DNMT3B (HGNC:2979): (DNA methyltransferase 3 beta) CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase which is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes primarily to the nucleus and its expression is developmentally regulated. Mutations in this gene cause the immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. Eight alternatively spliced transcript variants have been described. The full length sequences of variants 4 and 5 have not been determined. [provided by RefSeq, May 2011]

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 (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMT3B	NM_006892.4	c.432+87A>G		intron_variant		ENST00000328111.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT3B	ENST00000328111.6	c.432+87A>G		intron_variant		1	NM_006892.4	A2

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92843 AN: 152098 Hom.: 31717 Cov.: 33

Gnomad AFR AF: 0.892

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.556

GnomAD4 exome AF: 0.497 AC: 716584 AN: 1442126 Hom.: 190605 AF XY: 0.498 AC XY: 357871 AN XY: 718034

Gnomad4 AFR exome AF: 0.904

Gnomad4 AMR exome AF: 0.719

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.657

Gnomad4 FIN exome AF: 0.455

Gnomad4 NFE exome AF: 0.445

Gnomad4 OTH exome AF: 0.536

GnomAD4 genome AF: 0.611 AC: 92968 AN: 152216 Hom.: 31781 Cov.: 33 AF XY: 0.615 AC XY: 45758 AN XY: 74420

Gnomad4 AFR AF: 0.893

Gnomad4 AMR AF: 0.604

Gnomad4 ASJ AF: 0.512

Gnomad4 EAS AF: 0.993

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.453

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.556

Alfa AF: 0.494 Hom.: 9309

Bravo AF: 0.636

Asia WGS AF: 0.846 AC: 2941 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	11
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2424914; hg19: chr20-31374520;