rs7253062

Positions:

• chr19-10184448-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.81-2371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,002 control chromosomes in the GnomAD database, including 9,539 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 0.34 (9539 hom., cov: 31)
  • Exomes 𝑓: 0.38 (0 hom.)
• Consequence: DNMT1 NM_001130823.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNMT1	NM_001130823.3	c.81-2371C>T		intron_variant		ENST00000359526.9
DNMT1	NM_001318730.2	c.81-2371C>T		intron_variant
DNMT1	NM_001318731.2	c.-243-2371C>T		intron_variant
DNMT1	NM_001379.4	c.81-2371C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT1	ENST00000359526.9	c.81-2371C>T		intron_variant		1	NM_001130823.3

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52162 AN: 151868 Hom.: 9540 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.375 AC: 6 AN: 16 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 2 AN XY: 8

Gnomad4 AFR exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.250

GnomAD4 genome AF: 0.343 AC: 52178 AN: 151986 Hom.: 9539 Cov.: 31 AF XY: 0.339 AC XY: 25154 AN XY: 74284

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.443

Gnomad4 EAS AF: 0.238

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.416

Gnomad4 OTH AF: 0.345

Alfa AF: 0.393 Hom.: 5593

Bravo AF: 0.328

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.60
DANN	Benign	0.46

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: rs7253062; hg19: chr19-10295124;