rs11880388

Positions:

• chr19-10142897-G-A

Variant summary

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

The NM_001130823.3(DNMT1):​c.3117-677C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 157,454 control chromosomes in the GnomAD database, including 18,845 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 0.49 (18235 hom., cov: 32)
  • Exomes 𝑓: 0.47 (610 hom.)
• Consequence: DNMT1 NM_001130823.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377

Genes affected

DNMT1 (HGNC:2976): (DNA methyltransferase 1) This gene encodes an enzyme that transfers methyl groups to cytosine nucleotides of genomic DNA. This protein is the major enzyme responsible for maintaining methylation patterns following DNA replication and shows a preference for hemi-methylated DNA. Methylation of DNA is an important component of mammalian epigenetic gene regulation. Aberrant methylation patterns are found in human tumors and associated with developmental abnormalities. Variation in this gene has been associated with cerebellar ataxia, deafness, and narcolepsy, and neuropathy, hereditary sensory, type IE. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT1	NM_001130823.3	c.3117-677C>T		intron_variant		ENST00000359526.9	NP_001124295.1
DNMT1	NM_001318730.2	c.3069-677C>T		intron_variant			NP_001305659.1
DNMT1	NM_001318731.2	c.2754-677C>T		intron_variant			NP_001305660.1
DNMT1	NM_001379.4	c.3069-677C>T		intron_variant			NP_001370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT1	ENST00000359526.9	c.3117-677C>T		intron_variant		1	NM_001130823.3	ENSP00000352516

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74009 AN: 151966 Hom.: 18241 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.513

GnomAD4 exome AF: 0.468 AC: 2515 AN: 5370 Hom.: 610 Cov.: 0 AF XY: 0.465 AC XY: 1338 AN XY: 2878

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.273

Gnomad4 SAS exome AF: 0.434

Gnomad4 FIN exome AF: 0.478

Gnomad4 NFE exome AF: 0.476

Gnomad4 OTH exome AF: 0.473

GnomAD4 genome AF: 0.487 AC: 74030 AN: 152084 Hom.: 18235 Cov.: 32 AF XY: 0.486 AC XY: 36146 AN XY: 74344

Gnomad4 AFR AF: 0.481

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.509

Alfa AF: 0.453 Hom.: 3584

Bravo AF: 0.492

Asia WGS AF: 0.413 AC: 1436 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	2.1
DANN	Benign	0.66

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: rs11880388; hg19: chr19-10253573;