rs10418707

Positions:

• chr19-10145541-G-A
• chr19-10145541-G-C
• chr19-10145541-G-T

Variant summary

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

The NM_001130823.3(DNMT1):​c.2894+810C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,238 control chromosomes in the GnomAD database, including 1,402 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 0.11 (1402 hom., cov: 32)
• Consequence: DNMT1 NM_001130823.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT1	NM_001130823.3	c.2894+810C>T		intron_variant		ENST00000359526.9	NP_001124295.1
DNMT1	NM_001318730.2	c.2846+810C>T		intron_variant			NP_001305659.1
DNMT1	NM_001318731.2	c.2531+810C>T		intron_variant			NP_001305660.1
DNMT1	NM_001379.4	c.2846+810C>T		intron_variant			NP_001370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT1	ENST00000359526.9	c.2894+810C>T		intron_variant		1	NM_001130823.3	ENSP00000352516

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17042 AN: 152120 Hom.: 1399 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0626

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.112 AC: 17075 AN: 152238 Hom.: 1402 Cov.: 32 AF XY: 0.118 AC XY: 8796 AN XY: 74450

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0926

Gnomad4 NFE AF: 0.0626

Gnomad4 OTH AF: 0.108

Alfa AF: 0.0744 Hom.: 591

Bravo AF: 0.121

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.80
DANN	Benign	0.75

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: rs10418707; hg19: chr19-10256217;