rs8112895

Positions:

• chr19-10194486-A-G

Variant summary

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

The NM_001130823.3(DNMT1):​c.80+334T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 221,016 control chromosomes in the GnomAD database, including 2,871 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 0.14 (2115 hom., cov: 32)
  • Exomes 𝑓: 0.11 (756 hom.)
• Consequence: DNMT1 NM_001130823.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNMT1	NM_001130823.3	c.80+334T>C		intron_variant		ENST00000359526.9	NP_001124295.1
DNMT1	NM_001318730.2	c.80+334T>C		intron_variant			NP_001305659.1
DNMT1	NM_001318731.2	c.-244+334T>C		intron_variant			NP_001305660.1
DNMT1	NM_001379.4	c.80+334T>C		intron_variant			NP_001370.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT1	ENST00000359526.9	c.80+334T>C		intron_variant		1	NM_001130823.3	ENSP00000352516

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21136 AN: 152112 Hom.: 2094 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0644

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.107 AC: 7381 AN: 68786 Hom.: 756 Cov.: 2 AF XY: 0.110 AC XY: 3878 AN XY: 35176

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.176

Gnomad4 ASJ exome AF: 0.0943

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.112

Gnomad4 NFE exome AF: 0.0587

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.139 AC: 21215 AN: 152230 Hom.: 2115 Cov.: 32 AF XY: 0.147 AC XY: 10906 AN XY: 74430

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0644

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0963 Hom.: 171

Bravo AF: 0.147

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.51

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: rs8112895; hg19: chr19-10305162;