chr18-50273773-G-C

Variant names:

• chr18-50273773-G-C
• NM_015846.4:c.1237C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015846.4(MBD1):​c.1237C>G​(p.Arg413Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,730 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MBD1 NM_015846.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24388462).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBD1	NM_015846.4	c.1237C>G	p.Arg413Gly	missense_variant	Exon 12 of 17	ENST00000269468.10	NP_056671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD1	ENST00000269468.10	c.1237C>G	p.Arg413Gly	missense_variant	Exon 12 of 17	5	NM_015846.4	ENSP00000269468.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461730 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727162

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	.;T;.;T;.;T;.;.;.;.;.;.;T;T;.;.;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.96	D;.;D;.;D;D;D;D;D;D;.;.;D;D;D;.;D;D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.24	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.42	D
MutationAssessor	Uncertain	2.3	.;M;.;M;M;M;.;.;M;.;.;.;.;.;.;.;.;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	.;N;N;.;N;N;N;N;.;.;.;.;.;.;N;N;N;.
REVEL	Uncertain	0.34
Sift	Benign	0.22	.;T;T;.;T;T;T;D;.;.;.;.;.;.;T;D;D;.
Sift4G	Uncertain	0.032	D;D;D;D;T;D;T;T;D;T;T;D;D;T;D;T;T;T
Polyphen		0.47, 0.61, 0.80, 0.96, 0.89, 0.71, 0.76	.;P;P;P;P;P;D;P;.;.;D;.;.;.;.;P;P;P
Vest4		0.27
MVP		0.72
MPC		0.82
ClinPred		0.25	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.076
gMVP		0.39

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-47800143;