19-1586218-G-A

Variant names:

• chr19-1586218-G-A
• rs4807934
• NM_001281453.2:c.111-1004C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281453.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	NM_001281453.2	MANE Select	c.111-1004C>T		intron	N/A	NP_001268382.1
	MBD3	NM_001281454.2		c.15-1004C>T		intron	N/A	NP_001268383.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD3	ENST00000434436.8	TSL:1 MANE Select	c.111-1004C>T		intron	N/A	ENSP00000412302.2
	MBD3	ENST00000156825.5	TSL:1	c.15-1004C>T		intron	N/A	ENSP00000156825.2
	ENSG00000267059	ENST00000585937.1	TSL:3	n.*29-1004C>T		intron	N/A	ENSP00000468614.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.289 AC: 11 AN: 38

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.38
DANN	Benign	0.60
PhyloP100		-3.1
PromoterAI		0.021	Neutral
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: rs4807934; hg19: chr19-1586217;