Variant chr18-50276984-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_015846.4(MBD1):c.240G>A(p.Ala80=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,614,128 control chromosomes in the GnomAD database, including 18,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.10 ( 1902 hom., cov: 33)

Exomes 𝑓: 0.11 ( 16119 hom. )

Consequence

MBD1
NM_015846.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.346

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP7

Synonymous conserved (PhyloP=-0.346 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBD1	NM_015846.4 linkuse as main transcript	c.240G>A	p.Ala80=	synonymous_variant	4/17	ENST00000269468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBD1	ENST00000269468.10 linkuse as main transcript	c.240G>A	p.Ala80=	synonymous_variant	4/17	5	NM_015846.4		Q9UIS9-1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15913

AN:

152134

Hom.:

1896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.223

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.595

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.0944

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0785

Gnomad OTH

AF:

0.130

GnomAD3 exomes

AF:

0.172

AC:

43162

AN:

251468

Hom.:

6657

AF XY:

0.169

AC XY:

22950

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.302

Gnomad ASJ exome

AF:

0.116

Gnomad EAS exome

AF:

0.607

Gnomad SAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.0945

Gnomad NFE exome

AF:

0.0842

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.108

AC:

157403

AN:

1461876

Hom.:

16119

Cov.:

AF XY:

0.111

AC XY:

80769

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.291

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.587

Gnomad4 SAS exome

AF:

0.246

Gnomad4 FIN exome

AF:

0.0966

Gnomad4 NFE exome

AF:

0.0740

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

AF:

0.105

AC:

15935

AN:

152252

Hom.:

1902

Cov.:

AF XY:

0.113

AC XY:

8376

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0248

Gnomad4 AMR

AF:

0.223

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.595

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.0944

Gnomad4 NFE

AF:

0.0785

Gnomad4 OTH

AF:

0.131

Alfa

AF:

0.0839

Hom.:

1010

Bravo

AF:

0.113

Asia WGS

AF:

0.390

AC:

1353

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

4.0

DANN

Benign

0.39

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over