Variant rs2241531 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001130823.3(DNMT1):c.1043+26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,613,140 control chromosomes in the GnomAD database, including 13,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2143 hom., cov: 33)

Exomes 𝑓: 0.096 ( 11196 hom. )

Consequence

DNMT1
NM_001130823.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.602

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 19-10160358-C-G is Benign according to our data. Variant chr19-10160358-C-G is described in ClinVar as [Benign]. Clinvar id is 1246124.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DNMT1	NM_001130823.3 link	c.1043+26G>C	intron_variant	ENST00000359526.9	NP_001124295.1	P26358-2I6L9H2
DNMT1	NM_001318730.2 link	c.995+26G>C	intron_variant		NP_001305659.1	P26358Q59FP7I6L9H2
DNMT1	NM_001379.4 link	c.995+26G>C	intron_variant		NP_001370.1	P26358-1I6L9H2
DNMT1	NM_001318731.2 link	c.680+26G>C	intron_variant		NP_001305660.1	P26358I6L9H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNMT1	ENST00000359526.9 link	c.1043+26G>C		intron_variant		1	NM_001130823.3	ENSP00000352516.3		P26358-2

Frequencies

GnomAD3 genomes

AF:

0.140

AC:

21256

AN:

152076

Hom.:

2122

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.0725

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.0644

Gnomad OTH

AF:

0.128

GnomAD3 exomes

AF:

0.153

AC:

38540

AN:

251248

Hom.:

4669

AF XY:

0.149

AC XY:

20244

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.237

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.466

Gnomad SAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.0624

Gnomad OTH exome

AF:

0.120

GnomAD4 exome

AF:

0.0960

AC:

140223

AN:

1460946

Hom.:

11196

Cov.:

AF XY:

0.0984

AC XY:

71550

AN XY:

726790

show subpopulations

Gnomad4 AFR exome

AF:

0.205

Gnomad4 AMR exome

AF:

0.235

Gnomad4 ASJ exome

AF:

0.112

Gnomad4 EAS exome

AF:

0.413

Gnomad4 SAS exome

AF:

0.206

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.0638

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.140

AC:

21335

AN:

152194

Hom.:

2143

Cov.:

AF XY:

0.148

AC XY:

10984

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.200

Gnomad4 AMR

AF:

0.201

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.442

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.0645

Gnomad4 OTH

AF:

0.129

Alfa

AF:

0.0577

Hom.:

Bravo

AF:

0.148

Asia WGS

AF:

0.323

AC:

1124

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

-0.93

CADD

Benign

1.0

DANN

Benign

0.59

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