chr18-50276984-C-T

Variant names:

• chr18-50276984-C-T
• rs140686
• NM_015846.4:c.240G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015846.4(MBD1):​c.240G>A​(p.Ala80Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,614,128 control chromosomes in the GnomAD database, including 18,021 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 0.10 (1902 hom., cov: 33)
  • Exomes 𝑓: 0.11 (16119 hom.)
• Consequence: MBD1 NM_015846.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 16 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=-0.346 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 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.240G>A	p.Ala80Ala	synonymous	Exon 4 of 17	NP_056671.2
	MBD1	NM_001323942.2		c.240G>A	p.Ala80Ala	synonymous	Exon 4 of 17	NP_001310871.1	A0A994J7H0
	MBD1	NM_001323947.2		c.240G>A	p.Ala80Ala	synonymous	Exon 4 of 17	NP_001310876.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD1	ENST00000269468.10	TSL:5 MANE Select	c.240G>A	p.Ala80Ala	synonymous	Exon 4 of 17	ENSP00000269468.5	Q9UIS9-1
	MBD1	ENST00000590208.5	TSL:1	c.240G>A	p.Ala80Ala	synonymous	Exon 4 of 16	ENSP00000468785.1	Q9UIS9-12
	MBD1	ENST00000588937.5	TSL:1	c.240G>A	p.Ala80Ala	synonymous	Exon 3 of 13	ENSP00000467763.1	Q9UIS9-2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15913 AN: 152134 Hom.: 1896 Cov.: 33

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.130

GnomAD2 exomes AF: 0.172 AC: 43162 AN: 251468 AF XY: 0.169

Gnomad AFR exome AF: 0.0233

Gnomad AMR exome AF: 0.302

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.607

Gnomad FIN exome AF: 0.0945

Gnomad NFE exome AF: 0.0842

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.108 AC: 157403 AN: 1461876 Hom.: 16119 Cov.: 36 AF XY: 0.111 AC XY: 80769 AN XY: 727244

African (AFR) AF: 0.0243 AC: 814 AN: 33480

American (AMR) AF: 0.291 AC: 13009 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 3088 AN: 26134

East Asian (EAS) AF: 0.587 AC: 23314 AN: 39700

South Asian (SAS) AF: 0.246 AC: 21244 AN: 86258

European-Finnish (FIN) AF: 0.0966 AC: 5158 AN: 53418

Middle Eastern (MID) AF: 0.159 AC: 918 AN: 5768

European-Non Finnish (NFE) AF: 0.0740 AC: 82257 AN: 1112000

Other (OTH) AF: 0.126 AC: 7601 AN: 60396

GnomAD4 genome AF: 0.105 AC: 15935 AN: 152252 Hom.: 1902 Cov.: 33 AF XY: 0.113 AC XY: 8376 AN XY: 74438

African (AFR) AF: 0.0248 AC: 1032 AN: 41554

American (AMR) AF: 0.223 AC: 3415 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3472

East Asian (EAS) AF: 0.595 AC: 3079 AN: 5174

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4820

European-Finnish (FIN) AF: 0.0944 AC: 1001 AN: 10604

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0785 AC: 5341 AN: 68012

Other (OTH) AF: 0.131 AC: 276 AN: 2114

Alfa AF: 0.0855 Hom.: 1310

Bravo AF: 0.113

Asia WGS AF: 0.390 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	4.0
DANN	Benign	0.39
PhyloP100		-0.35
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140686; hg19: chr18-47803354; COSMIC: COSV54006296; COSMIC: COSV54006296;