rs140689

Positions:

• chr18-50274051-A-T

Variant summary

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

The NM_015846.4(MBD1):​c.1146+135T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,386,462 control chromosomes in the GnomAD database, including 89,811 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 0.29 (7322 hom., cov: 32)
  • Exomes 𝑓: 0.36 (82489 hom.)
• Consequence: MBD1 NM_015846.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.400

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBD1	NM_015846.4	c.1146+135T>A		intron_variant		ENST00000269468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBD1	ENST00000269468.10	c.1146+135T>A		intron_variant		5	NM_015846.4

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44352 AN: 151944 Hom.: 7322 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.320

GnomAD4 exome AF: 0.355 AC: 438663 AN: 1234400 Hom.: 82489 AF XY: 0.355 AC XY: 221543 AN XY: 624106

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.329

Gnomad4 EAS exome AF: 0.0869

Gnomad4 SAS exome AF: 0.289

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.334

GnomAD4 genome AF: 0.292 AC: 44345 AN: 152062 Hom.: 7322 Cov.: 32 AF XY: 0.292 AC XY: 21705 AN XY: 74322

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.417

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.316

Alfa AF: 0.326 Hom.: 1075

Bravo AF: 0.273

Asia WGS AF: 0.179 AC: 624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs140689; hg19: chr18-47800421; COSMIC: COSV54004599; COSMIC: COSV54004599;