ENST00000339998.10:c.*189G>C

Variant names:

• chr18-50269822-C-G
• rs143072804
• ENST00000339998.10:c.*189G>C

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP6

The ENST00000339998.10(MBD1):​c.*189G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 803,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (0 hom.)
• Consequence: MBD1 ENST00000339998.10 3_prime_UTR
• Scores: Splicing: ADA: 0.0001771
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.955
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 18-50269822-C-G is Benign according to our data. Variant chr18-50269822-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3049833.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000339998.10. 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.*33-4G>C		splice_region intron	N/A	NP_056671.2
	MBD1	NM_001204137.2		c.*1679G>C		3_prime_UTR	Exon 17 of 17	NP_001191066.1	Q9UIS9-9
	MBD1	NM_001204138.2		c.*1679G>C		3_prime_UTR	Exon 17 of 17	NP_001191067.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD1	ENST00000339998.10	TSL:1	c.*189G>C		3_prime_UTR	Exon 14 of 14	ENSP00000339546.5	Q9UIS9-6
	MBD1	ENST00000269468.10	TSL:5 MANE Select	c.*33-4G>C		splice_region intron	N/A	ENSP00000269468.5	Q9UIS9-1
	MBD1	ENST00000590208.5	TSL:1	c.1779-4G>C		splice_region intron	N/A	ENSP00000468785.1	Q9UIS9-12

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152208 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000189 AC: 47 AN: 249032 AF XY: 0.000237

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000296

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000243 AC: 158 AN: 651344 Hom.: 0 Cov.: 7 AF XY: 0.000263 AC XY: 93 AN XY: 353500

African (AFR) AF: 0.0000554 AC: 1 AN: 18064

American (AMR) AF: 0.0000457 AC: 2 AN: 43772

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21102

East Asian (EAS) AF: 0.00 AC: 0 AN: 36174

South Asian (SAS) AF: 0.000242 AC: 17 AN: 70204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.000239 AC: 1 AN: 4178

European-Non Finnish (NFE) AF: 0.000345 AC: 128 AN: 370886

Other (OTH) AF: 0.000266 AC: 9 AN: 33820

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152326 Hom.: 0 Cov.: 32 AF XY: 0.0000805 AC XY: 6 AN XY: 74492

African (AFR) AF: 0.0000962 AC: 4 AN: 41588

American (AMR) AF: 0.00 AC: 0 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68024

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.000179 Hom.: 0

Bravo AF: 0.000200

EpiCase AF: 0.000600

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Likely 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	-0.51
CADD	Benign	15
DANN	Benign	0.85
PhyloP100		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00018
SpliceAI score (max)		0.12		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: rs143072804; hg19: chr18-47796192;