20-32786714-A-G

Variant names:

• chr20-32786714-A-G
• rs2424914
• NM_006892.4:c.432+87A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

DNMT3B Gene-Disease associations (from GenCC):

• immunodeficiency-centromeric instability-facial anomalies syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
• facioscapulohumeral muscular dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• immunodeficiency-centromeric instability-facial anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNMT3B	NM_006892.4	c.432+87A>G		intron_variant	Intron 5 of 22	ENST00000328111.6	NP_008823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMT3B	ENST00000328111.6	c.432+87A>G		intron_variant	Intron 5 of 22	1	NM_006892.4	ENSP00000328547.2

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

African (AFR) AF: 0.904 AC: 30055 AN: 33252

American (AMR) AF: 0.719 AC: 32023 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 13295 AN: 25996

East Asian (EAS) AF: 0.999 AC: 39539 AN: 39596

South Asian (SAS) AF: 0.657 AC: 56352 AN: 85758

European-Finnish (FIN) AF: 0.455 AC: 20663 AN: 45422

Middle Eastern (MID) AF: 0.462 AC: 2644 AN: 5720

European-Non Finnish (NFE) AF: 0.445 AC: 489887 AN: 1101958

Other (OTH) AF: 0.536 AC: 32126 AN: 59884

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

African (AFR) AF: 0.893 AC: 37093 AN: 41558

American (AMR) AF: 0.604 AC: 9234 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1776 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5143 AN: 5178

South Asian (SAS) AF: 0.688 AC: 3318 AN: 4826

European-Finnish (FIN) AF: 0.453 AC: 4794 AN: 10592

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29778 AN: 67976

Other (OTH) AF: 0.556 AC: 1175 AN: 2112

Alfa AF: 0.493 Hom.: 10188

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
PhyloP100		0.094
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2424914; hg19: chr20-31374520;