rs10418707

Variant names:

• chr19-10145541-G-A
• rs10418707
• NM_001130823.3:c.2894+810C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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]

DNMT1 Gene-Disease associations (from GenCC):

• autosomal dominant cerebellar ataxia, deafness and narcolepsy

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Genomics England PanelApp, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)
• hereditary sensory neuropathy-deafness-dementia syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DNMT1	NM_001130823.3	c.2894+810C>T		intron_variant	Intron 28 of 40	ENST00000359526.9	NP_001124295.1
DNMT1	NM_001318730.2	c.2846+810C>T		intron_variant	Intron 27 of 39		NP_001305659.1
DNMT1	NM_001379.4	c.2846+810C>T		intron_variant	Intron 27 of 39		NP_001370.1
DNMT1	NM_001318731.2	c.2531+810C>T		intron_variant	Intron 28 of 40		NP_001305660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNMT1	ENST00000359526.9	c.2894+810C>T		intron_variant	Intron 28 of 40	1	NM_001130823.3	ENSP00000352516.3

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

African (AFR) AF: 0.126 AC: 5220 AN: 41550

American (AMR) AF: 0.188 AC: 2875 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 373 AN: 3468

East Asian (EAS) AF: 0.394 AC: 2033 AN: 5156

South Asian (SAS) AF: 0.209 AC: 1007 AN: 4828

European-Finnish (FIN) AF: 0.0926 AC: 983 AN: 10616

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0626 AC: 4259 AN: 68028

Other (OTH) AF: 0.108 AC: 228 AN: 2112

Alfa AF: 0.0755 Hom.: 719

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
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10418707; hg19: chr19-10256217;