20-32787505-A-G

Position:

• chr20-32787505-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.654+54A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 1,568,548 control chromosomes in the GnomAD database, including 147,255 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 0.42 (14148 hom., cov: 33)
  • Exomes 𝑓: 0.42 (133107 hom.)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0610

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMT3B	NM_006892.4	c.654+54A>G		intron_variant		ENST00000328111.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT3B	ENST00000328111.6	c.654+54A>G		intron_variant		1	NM_006892.4	A2

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63097 AN: 151984 Hom.: 14127 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.921

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.393

GnomAD4 exome AF: 0.420 AC: 594635 AN: 1416446 Hom.: 133107 AF XY: 0.424 AC XY: 297789 AN XY: 702738

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.641

Gnomad4 ASJ exome AF: 0.423

Gnomad4 EAS exome AF: 0.914

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.384

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.415 AC: 63147 AN: 152102 Hom.: 14148 Cov.: 33 AF XY: 0.422 AC XY: 31381 AN XY: 74342

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.375

Gnomad4 OTH AF: 0.393

Alfa AF: 0.376 Hom.: 10152

Bravo AF: 0.425

Asia WGS AF: 0.680 AC: 2360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.37
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs4911108; hg19: chr20-31375311;