rs6119967

chr20-32804111-G-C

Variant summary

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

The NM_006892.4(DNMT3B):c.2232-1227G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,238 control chromosomes in the GnomAD database, including 1,229 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 0.073 (1229 hom., cov: 32)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMT3B	NM_006892.4	c.2232-1227G>C		intron_variant		ENST00000328111.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT3B	ENST00000328111.6	c.2232-1227G>C		intron_variant		1	NM_006892.4	A2

Frequencies

GnomAD3 genomes AF: 0.0727 AC: 11054 AN: 152120 Hom.: 1222 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0336

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.00325

Gnomad OTH AF: 0.0685

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

GnomAD4 genome AF: 0.0729 AC: 11093 AN: 152238 Hom.: 1229 Cov.: 32 AF XY: 0.0708 AC XY: 5270 AN XY: 74458

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0336

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00325

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0592 Hom.: 108

Bravo AF: 0.0843

Asia WGS AF: 0.0220 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.041
Dann	Benign	0.43

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: rs6119967; hg19: chr20-31391917;