dbSNP rs4807934: MBD3:c.111-1004C>T (chr19-1586218-G-A) – 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.111-1004C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 152,134 control chromosomes in the GnomAD database, including 18,464 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 0.48 ( 18461 hom., cov: 32)

Exomes 𝑓: 0.26 ( 3 hom. )

Consequence

MBD3
NM_001281453.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.15

Publications

3 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:

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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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MBD3	NM_001281453.2 link	c.111-1004C>T	intron_variant	Intron 1 of 6	ENST00000434436.8	NP_001268382.1	O95983-1
MBD3	NM_001281454.2 link	c.15-1004C>T	intron_variant	Intron 1 of 6		NP_001268383.1	O95983-2
MBD3	XM_047438939.1 link	c.111-1004C>T	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.111-1004C>T		intron_variant	Intron 1 of 6	1	NM_001281453.2	ENSP00000412302.2		O95983-1
ENSG00000267059	ENST00000585937.1 link	n.*29-1004C>T		intron_variant	Intron 2 of 6	3		ENSP00000468614.1

Frequencies

GnomAD3 genomes

AF:

0.479

AC:

72829

AN:

151966

Hom.:

18441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.640

Gnomad AMI

AF:

0.384

Gnomad AMR

AF:

0.504

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.602

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.396

Gnomad OTH

AF:

0.491

GnomAD4 exome

AF:

0.260

AC:

AN:

Hom.:

Cov.:

AF XY:

0.225

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.289

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.479

AC:

72895

AN:

152084

Hom.:

18461

Cov.:

AF XY:

0.476

AC XY:

35412

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.639

AC:

26535

AN:

41504

American (AMR)

AF:

0.505

AC:

7698

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1492

AN:

3472

East Asian (EAS)

AF:

0.481

AC:

2492

AN:

5184

South Asian (SAS)

AF:

0.602

AC:

2902

AN:

4824

European-Finnish (FIN)

AF:

0.311

AC:

3292

AN:

10588

Middle Eastern (MID)

AF:

0.568

AC:

166

AN:

292

European-Non Finnish (NFE)

AF:

0.396

AC:

26937

AN:

67946

Other (OTH)

AF:

0.489

AC:

1032

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1882

3765

5647

7530

9412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.428

Hom.:

17617

Bravo

AF:

0.499

Asia WGS

AF:

0.564

AC:

1959

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.38

(source)

DANN

Benign

0.60

PhyloP100

-3.1

PromoterAI

0.021

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over