rs11663629

Variant names:

• chr18-50269259-C-A
• rs11663629
• NM_015846.4:c.*592G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-50269259-C-A
• chr18-50269259-C-G
• chr18-50269259-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MBD1	NM_015846.4	c.*592G>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000269468.10	NP_056671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD1	ENST00000269468.10	c.*592G>T		3_prime_UTR_variant	Exon 17 of 17	5	NM_015846.4	ENSP00000269468.5

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

African (AFR) AF: 0.793 AC: 15488 AN: 19530

American (AMR) AF: 0.937 AC: 5287 AN: 5642

Ashkenazi Jewish (ASJ) AF: 0.918 AC: 7341 AN: 8000

East Asian (EAS) AF: 0.965 AC: 8422 AN: 8726

South Asian (SAS) AF: 0.932 AC: 32719 AN: 35100

European-Finnish (FIN) AF: 0.911 AC: 5411 AN: 5942

Middle Eastern (MID) AF: 0.892 AC: 1843 AN: 2066

European-Non Finnish (NFE) AF: 0.898 AC: 746139 AN: 830510

Other (OTH) AF: 0.895 AC: 29974 AN: 33486

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

African (AFR) AF: 0.807 AC: 33461 AN: 41474

American (AMR) AF: 0.919 AC: 14056 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.913 AC: 3170 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5029 AN: 5166

South Asian (SAS) AF: 0.942 AC: 4543 AN: 4824

European-Finnish (FIN) AF: 0.922 AC: 9776 AN: 10606

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61222 AN: 68020

Other (OTH) AF: 0.885 AC: 1865 AN: 2108

Alfa AF: 0.895 Hom.: 261521

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
PhyloP100		0.72
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: rs11663629; hg19: chr18-47795629;