Variant 3-129433387-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001276270.2(MBD4):c.1394-140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 895,946 control chromosomes in the GnomAD database, including 3,986 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 1128 hom., cov: 32)

Exomes 𝑓: 0.032 ( 2858 hom. )

Consequence

MBD4
NM_001276270.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.232

Variant links:

Genes affected

MBD4 (HGNC:6919): (methyl-CpG binding domain 4, DNA glycosylase) 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 an MBD domain at the N-terminus that functions both in binding to methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]

MBD4 links:

IFT122 (HGNC:13556): (intraflagellar transport 122) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This cytoplasmic protein contains seven WD repeats and an AF-2 domain which function by recruiting coregulatory molecules and in transcriptional activation. Mutations in this gene cause cranioectodermal dysplasia-1. A related pseudogene is located on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

IFT122 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 3-129433387-C-T is Benign according to our data. Variant chr3-129433387-C-T is described in ClinVar as [Benign]. Clinvar id is 1294890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD4	NM_001276270.2 linkuse as main transcript	c.1394-140G>A		intron_variant		ENST00000429544.7	NP_001263199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD4	ENST00000429544.7 linkuse as main transcript	c.1394-140G>A		intron_variant		1	NM_001276270.2	ENSP00000394080	A2	O95243-2

Frequencies

GnomAD3 genomes

AF:

0.0747

AC:

11350

AN:

151862

Hom.:

1125

Cov.:

show subpopulations

Gnomad AFR

AF:

0.155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.146

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.402

Gnomad SAS

AF:

0.0363

Gnomad FIN

AF:

0.00408

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00377

Gnomad OTH

AF:

0.0609

GnomAD4 exome

AF:

0.0316

AC:

23516

AN:

743966

Hom.:

2858

Cov.:

AF XY:

0.0299

AC XY:

11618

AN XY:

388218

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.00479

Gnomad4 EAS exome

AF:

0.362

Gnomad4 SAS exome

AF:

0.0244

Gnomad4 FIN exome

AF:

0.00344

Gnomad4 NFE exome

AF:

0.00331

Gnomad4 OTH exome

AF:

0.0439

GnomAD4 genome

AF:

0.0749

AC:

11385

AN:

151980

Hom.:

1128

Cov.:

AF XY:

0.0786

AC XY:

5837

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.00548

Gnomad4 EAS

AF:

0.401

Gnomad4 SAS

AF:

0.0361

Gnomad4 FIN

AF:

0.00408

Gnomad4 NFE

AF:

0.00377

Gnomad4 OTH

AF:

0.0613

Alfa

AF:

0.0213

Hom.:

461

Bravo

AF:

0.0894

Asia WGS

AF:

0.181

AC:

630

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.1

DANN

Benign

0.64

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over