rs11663629

chr18-50269259-C-Achr18-50269259-C-Gchr18-50269259-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.*592G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 1,101,180 control chromosomes in the GnomAD database, including 442,754 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 0.88 (59439 hom., cov: 31)
  • Exomes 𝑓: 0.90 (383315 hom.)
• Consequence: MBD1 NM_015846.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBD1	NM_015846.4	c.*592G>T		3_prime_UTR_variant	17/17	ENST00000269468.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBD1	ENST00000269468.10	c.*592G>T		3_prime_UTR_variant	17/17	5	NM_015846.4

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134149 AN: 152060 Hom.: 59405 Cov.: 31

Gnomad AFR AF: 0.807

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.942

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.886

GnomAD4 exome AF: 0.898 AC: 852624 AN: 949002 Hom.: 383315 Cov.: 33 AF XY: 0.899 AC XY: 401320 AN XY: 446434

Gnomad4 AFR exome AF: 0.793

Gnomad4 AMR exome AF: 0.937

Gnomad4 ASJ exome AF: 0.918

Gnomad4 EAS exome AF: 0.965

Gnomad4 SAS exome AF: 0.932

Gnomad4 FIN exome AF: 0.911

Gnomad4 NFE exome AF: 0.898

Gnomad4 OTH exome AF: 0.895

GnomAD4 genome AF: 0.882 AC: 134234 AN: 152178 Hom.: 59439 Cov.: 31 AF XY: 0.887 AC XY: 65952 AN XY: 74394

Gnomad4 AFR AF: 0.807

Gnomad4 AMR AF: 0.919

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.973

Gnomad4 SAS AF: 0.942

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.900

Gnomad4 OTH AF: 0.885

Alfa AF: 0.900 Hom.: 126578

Bravo AF: 0.878

Asia WGS AF: 0.941 AC: 3275 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	6.1
Dann	Benign	0.66

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: rs11663629; hg19: chr18-47795629;