rs140687

Variant names:

• chr18-50276088-C-A
• rs140687
• NM_015846.4:c.517-107G>T

Your query was ambiguous. Multiple possible variants found:

• chr18-50276088-C-A
• chr18-50276088-C-G
• chr18-50276088-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.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
• Publications: 2 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 = 0.749 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015846.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD1	NM_015846.4	MANE Select	c.517-107G>T		intron	N/A	NP_056671.2
	MBD1	NM_001323942.2		c.517-107G>T		intron	N/A	NP_001310871.1	A0A994J7H0
	MBD1	NM_001323947.2		c.517-107G>T		intron	N/A	NP_001310876.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD1	ENST00000269468.10	TSL:5 MANE Select	c.517-107G>T		intron	N/A	ENSP00000269468.5	Q9UIS9-1
	MBD1	ENST00000590208.5	TSL:1	c.517-107G>T		intron	N/A	ENSP00000468785.1	Q9UIS9-12
	MBD1	ENST00000588937.5	TSL:1	c.517-107G>T		intron	N/A	ENSP00000467763.1	Q9UIS9-2

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

African (AFR) AF: 0.478 AC: 13879 AN: 29012

American (AMR) AF: 0.762 AC: 27285 AN: 35804

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 17602 AN: 24322

East Asian (EAS) AF: 0.737 AC: 25987 AN: 35250

South Asian (SAS) AF: 0.727 AC: 55472 AN: 76320

European-Finnish (FIN) AF: 0.725 AC: 26350 AN: 36358

Middle Eastern (MID) AF: 0.727 AC: 2805 AN: 3856

European-Non Finnish (NFE) AF: 0.695 AC: 669947 AN: 963300

Other (OTH) AF: 0.687 AC: 36861 AN: 53648

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

African (AFR) AF: 0.487 AC: 20209 AN: 41464

American (AMR) AF: 0.731 AC: 11183 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.720 AC: 2500 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3988 AN: 5186

South Asian (SAS) AF: 0.723 AC: 3487 AN: 4826

European-Finnish (FIN) AF: 0.725 AC: 7677 AN: 10590

Middle Eastern (MID) AF: 0.673 AC: 198 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47041 AN: 67978

Other (OTH) AF: 0.688 AC: 1453 AN: 2112

Alfa AF: 0.669 Hom.: 15600

Bravo AF: 0.643

Asia WGS AF: 0.703 AC: 2445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.31
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs140687; hg19: chr18-47802458; COSMIC: COSV54004201; COSMIC: COSV54004201;