Genetic Variant MBP:c.576+11173C>A (chr18-77005659-G-T) – 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+11173C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,236 control chromosomes in the GnomAD database, including 44,294 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 0.76 ( 44258 hom., cov: 32)

Exomes 𝑓: 0.77 ( 36 hom. )

Consequence

MBP
NM_001025101.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.25

Publications

14 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:

Genome browser will be placed here

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=-1.01).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.774 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+11173C>A	intron	N/A	NP_001020272.1
MBP	NM_001025081.2		c.255+4190C>A	intron	N/A	NP_001020252.1
MBP	NM_002385.3		c.255+4190C>A	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+11173C>A	intron	N/A	ENSP00000348273.2
MBP	ENST00000382582.7	TSL:1	c.255+4190C>A	intron	N/A	ENSP00000372025.3
MBP	ENST00000359645.7	TSL:1	c.255+4190C>A	intron	N/A	ENSP00000352667.3

Frequencies

GnomAD3 genomes

AF:

0.761

AC:

115672

AN:

152006

Hom.:

44233

Cov.:

show subpopulations

Gnomad AFR

AF:

0.775

Gnomad AMI

AF:

0.839

Gnomad AMR

AF:

0.786

Gnomad ASJ

AF:

0.778

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.543

Gnomad FIN

AF:

0.796

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.772

Gnomad OTH

AF:

0.759

GnomAD4 exome

AF:

0.772

AC:

AN:

114

Hom.:

Cov.:

AF XY:

0.782

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.875

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.821

AC:

AN:

Other (OTH)

AF:

0.400

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.553

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.761

AC:

115750

AN:

152122

Hom.:

44258

Cov.:

AF XY:

0.759

AC XY:

56456

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.775

AC:

32126

AN:

41472

American (AMR)

AF:

0.786

AC:

12022

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.778

AC:

2701

AN:

3472

East Asian (EAS)

AF:

0.534

AC:

2758

AN:

5166

South Asian (SAS)

AF:

0.543

AC:

2616

AN:

4816

European-Finnish (FIN)

AF:

0.796

AC:

8446

AN:

10604

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.772

AC:

52508

AN:

67990

Other (OTH)

AF:

0.756

AC:

1592

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1407

2814

4222

5629

7036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

852

1704

2556

3408

4260

<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:

0.767

Hom.:

190341

Bravo

AF:

0.763

Asia WGS

AF:

0.581

AC:

2022

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.36

(source)

DANN

Benign

0.48

PhyloP100

-1.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over