rs1883729

Variant names:

• chr20-32775387-G-A
• rs1883729
• NM_006892.4:c.-6-4931G>A

Your query was ambiguous. Multiple possible variants found:

• chr20-32775387-G-A
• chr20-32775387-G-C
• chr20-32775387-G-T

Variant summary

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

The NM_006892.4(DNMT3B):​c.-6-4931G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,116 control chromosomes in the GnomAD database, including 27,225 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 0.56 (27225 hom., cov: 33)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNMT3B	NM_006892.4	c.-6-4931G>A		intron_variant	Intron 1 of 22	ENST00000328111.6	NP_008823.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMT3B	ENST00000328111.6	c.-6-4931G>A		intron_variant	Intron 1 of 22	1	NM_006892.4	ENSP00000328547.2

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85549 AN: 151998 Hom.: 27176 Cov.: 33

Gnomad AFR AF: 0.831

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.574

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.923

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.563 AC: 85654 AN: 152116 Hom.: 27225 Cov.: 33 AF XY: 0.567 AC XY: 42188 AN XY: 74352

African (AFR) AF: 0.831 AC: 34501 AN: 41530

American (AMR) AF: 0.575 AC: 8792 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1543 AN: 3472

East Asian (EAS) AF: 0.923 AC: 4776 AN: 5176

South Asian (SAS) AF: 0.656 AC: 3167 AN: 4826

European-Finnish (FIN) AF: 0.398 AC: 4206 AN: 10560

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27038 AN: 67944

Other (OTH) AF: 0.510 AC: 1076 AN: 2110

Alfa AF: 0.362 Hom.: 1101

Bravo AF: 0.589

Asia WGS AF: 0.750 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.0
DANN	Benign	0.81
PhyloP100		-0.91
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: rs1883729; hg19: chr20-31363193;