rs7252741

Positions:

• chr19-1580335-T-C

Variant summary

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

The NM_001281453.2(MBD3):​c.677+757A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 152,080 control chromosomes in the GnomAD database, including 4,174 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 0.23 (4174 hom., cov: 32)
• Consequence: MBD3 NM_001281453.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD3	NM_001281453.2	c.677+757A>G		intron_variant		ENST00000434436.8	NP_001268382.1
MBD3	NM_001281454.2	c.581+757A>G		intron_variant			NP_001268383.1
MBD3	XM_047438939.1	c.677+757A>G		intron_variant			XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD3	ENST00000434436.8	c.677+757A>G		intron_variant		1	NM_001281453.2	ENSP00000412302	P1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35037 AN: 151962 Hom.: 4168 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.214

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.231 AC: 35075 AN: 152080 Hom.: 4174 Cov.: 32 AF XY: 0.232 AC XY: 17283 AN XY: 74354

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.214

Alfa AF: 0.207 Hom.: 5308

Bravo AF: 0.232

Asia WGS AF: 0.257 AC: 891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.91
DANN	Benign	0.41

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: rs7252741; hg19: chr19-1580334;