rs140687

Positions:

• chr18-50276088-C-A
• chr18-50276088-C-G
• chr18-50276088-C-T

Variant summary

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

The NM_015846.4(MBD1):​c.517-107G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 1,409,992 control chromosomes in the GnomAD database, including 338,721 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 0.65 (32629 hom., cov: 33)
  • Exomes 𝑓: 0.70 (306092 hom.)
• Consequence: MBD1 NM_015846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42

Genes affected

MBD1 (HGNC:6916): (methyl-CpG binding domain protein 1) The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains multiple domains: MBD at the N-terminus that functions both in binding to methylated DNA and in protein interactions; several CXXC-type zinc finger domains that mediate binding to non-methylated CpG dinucleotides; transcriptional repression domain (TRD) at the C-terminus that is involved in transcription repression and in protein interactions. Numerous alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Feb 2011]

MBD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD1	NM_015846.4	c.517-107G>T		intron_variant		ENST00000269468.10	NP_056671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD1	ENST00000269468.10	c.517-107G>T		intron_variant		5	NM_015846.4	ENSP00000269468.5

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98377 AN: 152004 Hom.: 32611 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.758

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.720

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.692

GnomAD4 exome AF: 0.697 AC: 876188 AN: 1257870 Hom.: 306092 Cov.: 18 AF XY: 0.698 AC XY: 437819 AN XY: 627512

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.762

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.737

Gnomad4 SAS exome AF: 0.727

Gnomad4 FIN exome AF: 0.725

Gnomad4 NFE exome AF: 0.695

Gnomad4 OTH exome AF: 0.687

GnomAD4 genome AF: 0.647 AC: 98427 AN: 152122 Hom.: 32629 Cov.: 33 AF XY: 0.652 AC XY: 48467 AN XY: 74374

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.731

Gnomad4 ASJ AF: 0.720

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.725

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.688

Alfa AF: 0.670 Hom.: 13674

Bravo AF: 0.643

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs140687; hg19: chr18-47802458; COSMIC: COSV54004201; COSMIC: COSV54004201;