18-76980454-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001025101.2(MBP):​c.888C>T​(p.Arg296=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,562 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000010 ( 1 hom. )

Consequence

MBP
NM_001025101.2 synonymous

Scores

4
12

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.434
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.09598753).
BP6
Variant 18-76980454-G-A is Benign according to our data. Variant chr18-76980454-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 756077.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.434 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MBPNM_001025101.2 linkuse as main transcriptc.888C>T p.Arg296= synonymous_variant 9/9 ENST00000355994.7
LOC105372217XR_001753507.3 linkuse as main transcriptn.26G>A non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MBPENST00000355994.7 linkuse as main transcriptc.888C>T p.Arg296= synonymous_variant 9/95 NM_001025101.2 P1P02686-1
ENST00000582763.1 linkuse as main transcriptn.232+1257G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248756
Hom.:
0
AF XY:
0.0000297
AC XY:
4
AN XY:
134652
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000180
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461562
Hom.:
1
Cov.:
30
AF XY:
0.0000165
AC XY:
12
AN XY:
727094
show subpopulations
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:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJul 03, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.019
T
BayesDel_noAF
Uncertain
-0.030
CADD
Benign
4.6
DANN
Benign
0.92
DEOGEN2
Benign
0.035
T
Eigen
Benign
-0.20
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.26
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.096
T
MetaSVM
Benign
-0.76
T
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;N
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.026
Sift
Uncertain
0.0080
D
Sift4G
Uncertain
0.016
D
Vest4
0.12
MutPred
0.36
Gain of sheet (P = 0.0028);
MVP
0.29
ClinPred
0.24
T
GERP RS
-2.9

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.

Other links and lift over

dbSNP: rs761965498; hg19: chr18-74692410; API