ENST00000590208.5:c.1950C>T

Variant names:

• chr18-50269647-G-A
• rs72923678
• ENST00000590208.5:c.1950C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The ENST00000590208.5(MBD1):​c.1950C>T​(p.Cys650Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00553 in 745,532 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0046 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0058 (18 hom.)
• Consequence: MBD1 ENST00000590208.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.917
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 18-50269647-G-A is Benign according to our data. Variant chr18-50269647-G-A is described in ClinVar as Benign. ClinVar VariationId is 3060893.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.917 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000590208.5. 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.*204C>T		3_prime_UTR	Exon 17 of 17	NP_056671.2
	MBD1	NM_001323942.2		c.2025C>T	p.Cys675Cys	synonymous	Exon 17 of 17	NP_001310871.1
	MBD1	NM_001323947.2		c.1980C>T	p.Cys660Cys	synonymous	Exon 17 of 17	NP_001310876.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD1	ENST00000590208.5	TSL:1	c.1950C>T	p.Cys650Cys	synonymous	Exon 16 of 16	ENSP00000468785.1
	MBD1	ENST00000588937.5	TSL:1	c.1743C>T	p.Cys581Cys	synonymous	Exon 13 of 13	ENSP00000467763.1
	MBD1	ENST00000269468.10	TSL:5 MANE Select	c.*204C>T		3_prime_UTR	Exon 17 of 17	ENSP00000269468.5

Frequencies

GnomAD3 genomes AF: 0.00458 AC: 697 AN: 152154 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00126

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00556

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00786

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00495 AC: 967 AN: 195234 AF XY: 0.00501

Gnomad AFR exome AF: 0.00193

Gnomad AMR exome AF: 0.00221

Gnomad ASJ exome AF: 0.000221

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00655

Gnomad NFE exome AF: 0.00855

Gnomad OTH exome AF: 0.00484

GnomAD4 exome AF: 0.00578 AC: 3427 AN: 593260 Hom.: 18 Cov.: 0 AF XY: 0.00562 AC XY: 1808 AN XY: 321540

African (AFR) AF: 0.00131 AC: 22 AN: 16836

American (AMR) AF: 0.00226 AC: 87 AN: 38536

Ashkenazi Jewish (ASJ) AF: 0.000246 AC: 5 AN: 20312

East Asian (EAS) AF: 0.00 AC: 0 AN: 34476

South Asian (SAS) AF: 0.00141 AC: 93 AN: 65930

European-Finnish (FIN) AF: 0.00631 AC: 322 AN: 51028

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4100

European-Non Finnish (NFE) AF: 0.00831 AC: 2746 AN: 330260

Other (OTH) AF: 0.00475 AC: 151 AN: 31782

GnomAD4 genome AF: 0.00458 AC: 697 AN: 152272 Hom.: 3 Cov.: 32 AF XY: 0.00438 AC XY: 326 AN XY: 74450

African (AFR) AF: 0.00125 AC: 52 AN: 41554

American (AMR) AF: 0.00229 AC: 35 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4828

European-Finnish (FIN) AF: 0.00556 AC: 59 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00786 AC: 535 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00596 Hom.: 1

Bravo AF: 0.00435

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MBD1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs72923678; hg19: chr18-47796017;