Variant rs140692 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_001276270.2(MBD4):c.335+27T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,501,376 control chromosomes in the GnomAD database, including 11,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1678 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9630 hom. )

Consequence

MBD4
NM_001276270.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.665

Variant links:

Genes affected

MBD4 (HGNC:6919): (methyl-CpG binding domain 4, DNA glycosylase) The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains an MBD domain at the N-terminus that functions both in binding to methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

MBD4 links:

MBD4 (HGNC:):

MBD4 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=-0.84).

BP6

Variant 3-129437693-A-G is Benign according to our data. Variant chr3-129437693-A-G is described in ClinVar as [Benign]. Clinvar id is 1249121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD4	NM_001276270.2 linkuse as main transcript	c.335+27T>C		intron_variant		ENST00000429544.7	NP_001263199.1	O95243-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD4	ENST00000429544.7 linkuse as main transcript	c.335+27T>C		intron_variant		1	NM_001276270.2	ENSP00000394080.2		O95243-2

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20018

AN:

152096

Hom.:

1673

Cov.:

show subpopulations

Gnomad AFR

AF:

0.217

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.0813

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.0394

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0944

Gnomad OTH

AF:

0.142

GnomAD3 exomes

AF:

0.116

AC:

29218

AN:

251208

Hom.:

2326

AF XY:

0.123

AC XY:

16699

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.0703

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.0770

Gnomad SAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.0394

Gnomad NFE exome

AF:

0.0961

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.108

AC:

145580

AN:

1349162

Hom.:

9630

Cov.:

AF XY:

0.113

AC XY:

76273

AN XY:

677342

show subpopulations

Gnomad4 AFR exome

AF:

0.225

Gnomad4 AMR exome

AF:

0.0736

Gnomad4 ASJ exome

AF:

0.167

Gnomad4 EAS exome

AF:

0.0641

Gnomad4 SAS exome

AF:

0.246

Gnomad4 FIN exome

AF:

0.0417

Gnomad4 NFE exome

AF:

0.0970

Gnomad4 OTH exome

AF:

0.121

GnomAD4 genome

AF:

0.132

AC:

20047

AN:

152214

Hom.:

1678

Cov.:

AF XY:

0.131

AC XY:

9766

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.217

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.0807

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.0394

Gnomad4 NFE

AF:

0.0945

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.128

Hom.:

384

Bravo

AF:

0.138

Asia WGS

AF:

0.205

AC:

715

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	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.8

DANN

Benign

0.55

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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