rs6119286

chr20-32807671-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_006892.4(DNMT3B):c.2421-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,588,240 control chromosomes in the GnomAD database, including 653 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.036 (154 hom., cov: 32)
  • Exomes 𝑓: 0.022 (499 hom.)
• Consequence: DNMT3B NM_006892.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.585

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 20-32807671-G-A is Benign according to our data. Variant chr20-32807671-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMT3B	NM_006892.4	c.2421-91G>A		intron_variant		ENST00000328111.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT3B	ENST00000328111.6	c.2421-91G>A		intron_variant		1	NM_006892.4	A2

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5412 AN: 152156 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0154

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0449

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0195

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0219 AC: 31403 AN: 1435966 Hom.: 499 AF XY: 0.0219 AC XY: 15706 AN XY: 715734

Gnomad4 AFR exome AF: 0.0856

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.00265

Gnomad4 EAS exome AF: 0.00101

Gnomad4 SAS exome AF: 0.0400

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.0205

Gnomad4 OTH exome AF: 0.0224

GnomAD4 genome AF: 0.0357 AC: 5437 AN: 152274 Hom.: 154 Cov.: 32 AF XY: 0.0359 AC XY: 2670 AN XY: 74458

Gnomad4 AFR AF: 0.0812

Gnomad4 AMR AF: 0.0153

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0446

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.0195

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0312 Hom.: 21

Bravo AF: 0.0368

Asia WGS AF: 0.0480 AC: 166 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	1.4
Dann	Benign	0.35

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: rs6119286; hg19: chr20-31395477;