18-50273809-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_015846.4(MBD1):c.1201C>G(p.Pro401Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,613,612 control chromosomes in the GnomAD database, including 32,536 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.18 ( 2606 hom., cov: 33)

Exomes 𝑓: 0.20 ( 29930 hom. )

Consequence

MBD1
NM_015846.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.120

Publications

45 publications found

Variant links:

Genes affected

MBD1 (HGNC:6916): (methyl-CpG binding domain protein 1) 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 multiple domains: MBD at the N-terminus that functions both in binding to methylated DNA and in protein interactions; several CXXC-type zinc finger domains that mediate binding to non-methylated CpG dinucleotides; transcriptional repression domain (TRD) at the C-terminus that is involved in transcription repression and in protein interactions. Numerous alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Feb 2011]

MBD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001339227).

BP6

Variant 18-50273809-G-C is Benign according to our data. Variant chr18-50273809-G-C is described in ClinVar as Benign. ClinVar VariationId is 3060114.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBD1	NM_015846.4 link	c.1201C>G	p.Pro401Ala	missense_variant	Exon 12 of 17	ENST00000269468.10	NP_056671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD1	ENST00000269468.10 link	c.1201C>G	p.Pro401Ala	missense_variant	Exon 12 of 17	5	NM_015846.4	ENSP00000269468.5

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27759

AN:

152044

Hom.:

2605

Cov.:

show subpopulations

Gnomad AFR

AF:

0.140

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.215

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.163

GnomAD2 exomes

AF:

0.194

AC:

48490

AN:

250456

AF XY:

0.195

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.179

Gnomad ASJ exome

AF:

0.203

Gnomad EAS exome

AF:

0.187

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.201

AC:

294376

AN:

1461450

Hom.:

29930

Cov.:

AF XY:

0.202

AC XY:

146789

AN XY:

727042

show subpopulations

African (AFR)

AF:

0.137

AC:

4592

AN:

33480

American (AMR)

AF:

0.176

AC:

7886

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

5172

AN:

26136

East Asian (EAS)

AF:

0.184

AC:

7320

AN:

39700

South Asian (SAS)

AF:

0.207

AC:

17858

AN:

86254

European-Finnish (FIN)

AF:

0.194

AC:

10273

AN:

52996

Middle Eastern (MID)

AF:

0.181

AC:

1046

AN:

5768

European-Non Finnish (NFE)

AF:

0.205

AC:

228076

AN:

1112002

Other (OTH)

AF:

0.201

AC:

12153

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

15720

31440

47159

62879

78599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7910

15820

23730

31640

39550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.183

AC:

27771

AN:

152162

Hom.:

2606

Cov.:

AF XY:

0.183

AC XY:

13634

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.140

AC:

5805

AN:

41508

American (AMR)

AF:

0.170

AC:

2595

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

669

AN:

3470

East Asian (EAS)

AF:

0.186

AC:

960

AN:

5168

South Asian (SAS)

AF:

0.213

AC:

1028

AN:

4820

European-Finnish (FIN)

AF:

0.196

AC:

2083

AN:

10602

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14054

AN:

67976

Other (OTH)

AF:

0.166

AC:

351

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1161

2323

3484

4646

5807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.190

Hom.:

2262

Bravo

AF:

0.176

TwinsUK

AF:

0.205

AC:

761

ALSPAC

AF:

0.206

AC:

792

ESP6500AA

AF:

0.137

AC:

604

ESP6500EA

AF:

0.197

AC:

1692

ExAC

AF:

0.192

AC:

23299

Asia WGS

AF:

0.220

AC:

765

AN:

3478

EpiCase

AF:

0.200

EpiControl

AF:

0.192

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MBD1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.14

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0

.;T;.;T;.;T;.;.;.;.;.;.;T;T;.;.;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.85

D;.;T;.;T;T;D;D;T;D;.;.;D;D;D;.;D;D

MetaRNN

Benign

0.0013

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.0

.;M;.;M;M;M;.;.;M;.;.;.;.;.;.;.;.;.

PhyloP100

0.12

PrimateAI

Benign

0.32

PROVEAN

Benign

0.0

.;N;N;.;N;N;N;N;.;.;.;.;.;.;N;N;N;.

REVEL

Benign

0.0

Sift

Pathogenic

0.0

.;D;T;.;D;D;T;T;.;.;.;.;.;.;D;T;D;.

Sift4G

Benign

0.065

T;D;T;D;D;D;T;D;D;D;T;D;D;D;D;D;D;T

Vest4

0.13

ClinPred

0.0086

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.033

gMVP

0.74

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over