rs7252741

Variant names:

• chr19-1580335-T-C
• rs7252741
• NM_001281453.2:c.677+757A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MBD3	NM_001281453.2	c.677+757A>G		intron_variant	Intron 5 of 6	ENST00000434436.8	NP_001268382.1
MBD3	NM_001281454.2	c.581+757A>G		intron_variant	Intron 5 of 6		NP_001268383.1
MBD3	XM_047438939.1	c.677+757A>G		intron_variant	Intron 5 of 5		XP_047294895.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD3	ENST00000434436.8	c.677+757A>G		intron_variant	Intron 5 of 6	1	NM_001281453.2	ENSP00000412302.2
ENSG00000267059	ENST00000585937.1	n.*595+757A>G		intron_variant	Intron 6 of 6	3		ENSP00000468614.1

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

African (AFR) AF: 0.260 AC: 10769 AN: 41486

American (AMR) AF: 0.223 AC: 3410 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3466

East Asian (EAS) AF: 0.392 AC: 2023 AN: 5166

South Asian (SAS) AF: 0.173 AC: 836 AN: 4820

European-Finnish (FIN) AF: 0.239 AC: 2529 AN: 10588

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14044 AN: 67968

Other (OTH) AF: 0.214 AC: 451 AN: 2110

Alfa AF: 0.211 Hom.: 8949

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7252741; hg19: chr19-1580334;