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18-50269647-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The ENST00000590208.5(MBD1):c.1950C>T(p.Cys650=) 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 (★).

Frequency

Genomes: 𝑓 0.0046 ( 3 hom., cov: 32)
Exomes 𝑓: 0.0058 ( 18 hom. )

Consequence

MBD1
ENST00000590208.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.917
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-50269647-G-A is Benign according to our data. Variant chr18-50269647-G-A is described in ClinVar as [Benign]. Clinvar id is 3060893.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.917 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MBD1NM_015846.4 linkuse as main transcriptc.*204C>T 3_prime_UTR_variant 17/17 ENST00000269468.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MBD1ENST00000269468.10 linkuse as main transcriptc.*204C>T 3_prime_UTR_variant 17/175 NM_015846.4 Q9UIS9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00458
AC:
697
AN:
152154
Hom.:
3
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.00495
AC:
967
AN:
195234
Hom.:
6
AF XY:
0.00501
AC XY:
523
AN XY:
104440
show subpopulations
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 SAS exome
AF:
0.00164
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
show subpopulations
Gnomad4 AFR exome
AF:
0.00131
Gnomad4 AMR exome
AF:
0.00226
Gnomad4 ASJ exome
AF:
0.000246
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00141
Gnomad4 FIN exome
AF:
0.00631
Gnomad4 NFE exome
AF:
0.00831
Gnomad4 OTH exome
AF:
0.00475
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00458
AC:
697
AN:
152272
Hom.:
3
Cov.:
32
AF XY:
0.00438
AC XY:
326
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00125
Gnomad4 AMR
AF:
0.00229
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00556
Gnomad4 NFE
AF:
0.00786
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00596
Hom.:
1
Bravo
AF:
0.00435
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

MBD1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 12, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.65
Cadd
Benign
13
Dann
Benign
0.68
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs72923678; hg19: chr18-47796017; API