dbSNP rs4807122: MBD3:c.111-1061G>A (chr19-1586275-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001281453.2(MBD3):c.111-1061G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,134 control chromosomes in the GnomAD database, including 24,704 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 0.54 ( 24698 hom., cov: 32)

Exomes 𝑓: 0.39 ( 6 hom. )

Consequence

MBD3
NM_001281453.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.252

Publications

4 publications found

Variant links:

Genes affected

MBD3 (HGNC:6918): (methyl-CpG binding domain protein 3) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. This gene belongs to a family of nuclear proteins which are characterized by the presence of a methyl-CpG binding domain (MBD). The encoded protein is a subunit of the NuRD, a multisubunit complex containing nucleosome remodeling and histone deacetylase activities. Unlike the other family members, the encoded protein is not capable of binding to methylated DNA. The protein mediates the association of metastasis-associated protein 2 with the core histone deacetylase complex. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013]

MBD3 links:

ENSG00000267059 (HGNC:):

ENSG00000267059 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBD3	NM_001281453.2 link	c.111-1061G>A	intron_variant	Intron 1 of 6	ENST00000434436.8	NP_001268382.1	O95983-1
MBD3	NM_001281454.2 link	c.15-1061G>A	intron_variant	Intron 1 of 6		NP_001268383.1	O95983-2
MBD3	XM_047438939.1 link	c.111-1061G>A	intron_variant	Intron 1 of 5		XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD3	ENST00000434436.8 link	c.111-1061G>A		intron_variant	Intron 1 of 6	1	NM_001281453.2	ENSP00000412302.2		O95983-1
ENSG00000267059	ENST00000585937.1 link	n.*29-1061G>A		intron_variant	Intron 2 of 6	3		ENSP00000468614.1

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82268

AN:

151952

Hom.:

24653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.383

Gnomad AMR

AF:

0.599

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.832

Gnomad SAS

AF:

0.677

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.401

Gnomad OTH

AF:

0.544

GnomAD4 exome

AF:

0.391

AC:

AN:

Hom.:

Cov.:

AF XY:

0.333

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.625

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.304

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.542

AC:

82372

AN:

152070

Hom.:

24698

Cov.:

AF XY:

0.542

AC XY:

40284

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.766

AC:

31765

AN:

41484

American (AMR)

AF:

0.599

AC:

9151

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

1635

AN:

3472

East Asian (EAS)

AF:

0.832

AC:

4304

AN:

5174

South Asian (SAS)

AF:

0.676

AC:

3253

AN:

4812

European-Finnish (FIN)

AF:

0.313

AC:

3311

AN:

10572

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.401

AC:

27281

AN:

67976

Other (OTH)

AF:

0.544

AC:

1148

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1726

3452

5179

6905

8631

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.465

Hom.:

33050

Bravo

AF:

0.571

Asia WGS

AF:

0.755

AC:

2622

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.3

(source)

DANN

Benign

0.78

PhyloP100

0.25

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over