Variant 18-50269647-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The ENST00000590208.5(MBD1):c.1950C>T(p.Cys650=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 745,532 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 18 hom. )

Consequence

MBD1
ENST00000590208.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.917

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 18-50269647-G-A is Benign according to our data. Variant chr18-50269647-G-A is described in ClinVar as [Benign]. Clinvar id is 3060893.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.917 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBD1	NM_015846.4 linkuse as main transcript	c.*204C>T		3_prime_UTR_variant	17/17	ENST00000269468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBD1	ENST00000269468.10 linkuse as main transcript	c.*204C>T		3_prime_UTR_variant	17/17	5	NM_015846.4		Q9UIS9-1

Frequencies

GnomAD3 genomes

AF:

0.00458

AC:

697

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00556

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00786

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00495

AC:

967

AN:

195234

Hom.:

AF XY:

0.00501

AC XY:

523

AN XY:

104440

show subpopulations

Gnomad AFR exome

AF:

0.00193

Gnomad AMR exome

AF:

0.00221

Gnomad ASJ exome

AF:

0.000221

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00164

Gnomad FIN exome

AF:

0.00655

Gnomad NFE exome

AF:

0.00855

Gnomad OTH exome

AF:

0.00484

GnomAD4 exome

AF:

0.00578

AC:

3427

AN:

593260

Hom.:

Cov.:

AF XY:

0.00562

AC XY:

1808

AN XY:

321540

show subpopulations

Gnomad4 AFR exome

AF:

0.00131

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.000246

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00141

Gnomad4 FIN exome

AF:

0.00631

Gnomad4 NFE exome

AF:

0.00831

Gnomad4 OTH exome

AF:

0.00475

GnomAD4 genome

AF:

0.00458

AC:

697

AN:

152272

Hom.:

Cov.:

AF XY:

0.00438

AC XY:

326

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00556

Gnomad4 NFE

AF:

0.00786

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00596

Hom.:

Bravo

AF:

0.00435

Asia WGS

AF:

0.000289

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

Jul 12, 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

-0.65

CADD

Benign

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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