rs4807122

Positions:

• chr19-1586275-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252

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]

ENSG00000267059 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD3	NM_001281453.2	c.111-1061G>A		intron_variant		ENST00000434436.8	NP_001268382.1
MBD3	NM_001281454.2	c.15-1061G>A		intron_variant			NP_001268383.1
MBD3	XM_047438939.1	c.111-1061G>A		intron_variant			XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD3	ENST00000434436.8	c.111-1061G>A		intron_variant		1	NM_001281453.2	ENSP00000412302.2
ENSG00000267059	ENST00000585937.1	n.*29-1061G>A		intron_variant		3		ENSP00000468614.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82268 AN: 151952 Hom.: 24653 Cov.: 32

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: 25 AN: 64 Hom.: 6 Cov.: 0 AF XY: 0.333 AC XY: 16 AN XY: 48

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.625

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.542 AC: 82372 AN: 152070 Hom.: 24698 Cov.: 32 AF XY: 0.542 AC XY: 40284 AN XY: 74338

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.599

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.544

Alfa AF: 0.453 Hom.: 7911

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
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs4807122; hg19: chr19-1586274;