Variant 18-50267603-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The ENST00000585672.5(MBD1):c.1689C>T(p.Ser563=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0579 in 1,533,968 control chromosomes in the GnomAD database, including 3,092 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.045 ( 226 hom., cov: 33)

Exomes 𝑓: 0.059 ( 2866 hom. )

Consequence

MBD1
ENST00000585672.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.29

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 made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 18-50267603-G-A is Benign according to our data. Variant chr18-50267603-G-A is described in ClinVar as [Benign]. Clinvar id is 3056934.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
MBD1	NM_001388147.1 linkuse as main transcript	c.1914C>T	p.Ser638=	synonymous_variant	17/17
MBD1	NM_001399883.1 linkuse as main transcript	c.1911C>T	p.Ser637=	synonymous_variant	17/17
MBD1	NM_001399889.1 linkuse as main transcript	c.1869C>T	p.Ser623=	synonymous_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
MBD1	ENST00000585672.5 linkuse as main transcript	c.1689C>T	p.Ser563=	synonymous_variant	15/15	1	Q9UIS9-10
MBD1	ENST00000592060.5 linkuse as main transcript	c.1236C>T	p.Ser412=	synonymous_variant	11/11	1
MBD1	ENST00000382948.9 linkuse as main transcript	c.*93C>T		3_prime_UTR_variant	17/17	2	Q9UIS9-1

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6852

AN:

152144

Hom.:

226

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0357

Gnomad ASJ

AF:

0.0669

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0137

Gnomad FIN

AF:

0.112

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0619

Gnomad OTH

AF:

0.0531

GnomAD3 exomes

AF:

0.0423

AC:

5691

AN:

134632

Hom.:

199

AF XY:

0.0409

AC XY:

2995

AN XY:

73314

show subpopulations

Gnomad AFR exome

AF:

0.0105

Gnomad AMR exome

AF:

0.0282

Gnomad ASJ exome

AF:

0.0581

Gnomad EAS exome

AF:

0.0000952

Gnomad SAS exome

AF:

0.0128

Gnomad FIN exome

AF:

0.118

Gnomad NFE exome

AF:

0.0628

Gnomad OTH exome

AF:

0.0499

GnomAD4 exome

AF:

0.0593

AC:

81915

AN:

1381708

Hom.:

2866

Cov.:

AF XY:

0.0580

AC XY:

39558

AN XY:

681920

show subpopulations

Gnomad4 AFR exome

AF:

0.00966

Gnomad4 AMR exome

AF:

0.0278

Gnomad4 ASJ exome

AF:

0.0565

Gnomad4 EAS exome

AF:

0.000168

Gnomad4 SAS exome

AF:

0.0123

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.0661

Gnomad4 OTH exome

AF:

0.0521

GnomAD4 genome

AF:

0.0450

AC:

6847

AN:

152260

Hom.:

226

Cov.:

AF XY:

0.0464

AC XY:

3452

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0114

Gnomad4 AMR

AF:

0.0356

Gnomad4 ASJ

AF:

0.0669

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.112

Gnomad4 NFE

AF:

0.0619

Gnomad4 OTH

AF:

0.0521

Alfa

AF:

0.0428

Hom.:

Bravo

AF:

0.0381

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

MBD1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 20, 2019

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

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.4

DANN

Benign

0.42

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