Variant rs4804490 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001130823.3(DNMT1):c.1399+56G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0948 in 1,410,962 control chromosomes in the GnomAD database, including 10,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1498 hom., cov: 31)

Exomes 𝑓: 0.092 ( 8586 hom. )

Consequence

DNMT1
NM_001130823.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.198

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 19-10156335-C-A is Benign according to our data. Variant chr19-10156335-C-A is described in ClinVar as [Benign]. Clinvar id is 1251118.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
DNMT1	NM_001130823.3 linkuse as main transcript	c.1399+56G>T	intron_variant	ENST00000359526.9
DNMT1	NM_001318730.2 linkuse as main transcript	c.1351+56G>T	intron_variant
DNMT1	NM_001318731.2 linkuse as main transcript	c.1036+56G>T	intron_variant
DNMT1	NM_001379.4 linkuse as main transcript	c.1351+56G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMT1	ENST00000359526.9 linkuse as main transcript	c.1399+56G>T		intron_variant		1	NM_001130823.3		P26358-2

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17797

AN:

151786

Hom.:

1493

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.191

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.397

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.0923

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.0628

Gnomad OTH

AF:

0.111

GnomAD4 exome

AF:

0.0921

AC:

115908

AN:

1259060

Hom.:

8586

AF XY:

0.0949

AC XY:

60341

AN XY:

636082

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.231

Gnomad4 ASJ exome

AF:

0.111

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.0850

Gnomad4 NFE exome

AF:

0.0625

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.117

AC:

17843

AN:

151902

Hom.:

1498

Cov.:

AF XY:

0.123

AC XY:

9140

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.192

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.398

Gnomad4 SAS

AF:

0.208

Gnomad4 FIN

AF:

0.0923

Gnomad4 NFE

AF:

0.0629

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.0426

Hom.:

Bravo

AF:

0.127

Asia WGS

AF:

0.264

AC:

917

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.2

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over