rs4807934

Positions:

• chr19-1586218-G-A
• chr19-1586218-G-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15

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]

ACMG classification

Verdict is Benign. Variant got -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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD3	NM_001281453.2	c.111-1004C>T		intron_variant		ENST00000434436.8	NP_001268382.1
MBD3	NM_001281454.2	c.15-1004C>T		intron_variant			NP_001268383.1
MBD3	XM_047438939.1	c.111-1004C>T		intron_variant			XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD3	ENST00000434436.8	c.111-1004C>T		intron_variant		1	NM_001281453.2	ENSP00000412302	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72829 AN: 151966 Hom.: 18441 Cov.: 32

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: 13 AN: 50 Hom.: 3 Cov.: 0 AF XY: 0.225 AC XY: 9 AN XY: 40

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.289

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.479 AC: 72895 AN: 152084 Hom.: 18461 Cov.: 32 AF XY: 0.476 AC XY: 35412 AN XY: 74340

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.602

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.489

Alfa AF: 0.413 Hom.: 12171

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
DANN	Benign	0.60

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: rs4807934; hg19: chr19-1586217;