Genetic Variant MBP:c.576+13267T>C (chr18-77003565-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001025101.2(MBP):c.576+13267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,188 control chromosomes in the GnomAD database, including 2,324 homozygotes. 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: 𝑓 0.16 ( 2324 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

MBP
NM_001025101.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0590

Publications

5 publications found

Variant links:

Genes affected

MBP (HGNC:6925): (myelin basic protein) The protein encoded by the classic MBP gene is a major constituent of the myelin sheath of oligodendrocytes and Schwann cells in the nervous system. However, MBP-related transcripts are also present in the bone marrow and the immune system. These mRNAs arise from the long MBP gene (otherwise called "Golli-MBP") that contains 3 additional exons located upstream of the classic MBP exons. Alternative splicing from the Golli and the MBP transcription start sites gives rise to 2 sets of MBP-related transcripts and gene products. The Golli mRNAs contain 3 exons unique to Golli-MBP, spliced in-frame to 1 or more MBP exons. They encode hybrid proteins that have N-terminal Golli aa sequence linked to MBP aa sequence. The second family of transcripts contain only MBP exons and produce the well characterized myelin basic proteins. This complex gene structure is conserved among species suggesting that the MBP transcription unit is an integral part of the Golli transcription unit and that this arrangement is important for the function and/or regulation of these genes. [provided by RefSeq, Jul 2008]

MBP links:

ENSG00000279811 (HGNC:):

ENSG00000279811 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025101.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MBP	NM_001025101.2	MANE Select	c.576+13267T>C	intron	N/A	NP_001020272.1
MBP	NM_001025081.2		c.255+6284T>C	intron	N/A	NP_001020252.1
MBP	NM_002385.3		c.255+6284T>C	intron	N/A	NP_002376.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MBP	ENST00000355994.7	TSL:5 MANE Select	c.576+13267T>C	intron	N/A	ENSP00000348273.2
MBP	ENST00000382582.7	TSL:1	c.255+6284T>C	intron	N/A	ENSP00000372025.3
MBP	ENST00000359645.7	TSL:1	c.255+6284T>C	intron	N/A	ENSP00000352667.3

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25021

AN:

152070

Hom.:

2315

Cov.:

show subpopulations

Gnomad AFR

AF:

0.255

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.0959

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0775

Gnomad SAS

AF:

0.195

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.131

Gnomad OTH

AF:

0.164

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.165

AC:

25065

AN:

152188

Hom.:

2324

Cov.:

AF XY:

0.164

AC XY:

12217

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.255

AC:

10586

AN:

41502

American (AMR)

AF:

0.0958

AC:

1465

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

558

AN:

3466

East Asian (EAS)

AF:

0.0771

AC:

399

AN:

5176

South Asian (SAS)

AF:

0.197

AC:

949

AN:

4820

European-Finnish (FIN)

AF:

0.145

AC:

1530

AN:

10586

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.131

AC:

8900

AN:

68018

Other (OTH)

AF:

0.167

AC:

354

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1053

2107

3160

4214

5267

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.141

Hom.:

2039

Bravo

AF:

0.164

Asia WGS

AF:

0.137

AC:

475

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.7

(source)

DANN

Benign

0.55

PhyloP100

0.059

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over