18-77089350-C-A

Variant names:

• chr18-77089350-C-A
• rs1026520
• NM_001025101.2:c.51+15861G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025101.2(MBP):​c.51+15861G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 152,194 control chromosomes in the GnomAD database, including 42,873 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 0.74 (42873 hom., cov: 34)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 9 publications found

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]

LOC124904328 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.87 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.51+15861G>T		intron_variant	Intron 2 of 8	ENST00000355994.7	NP_001020272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBP	ENST00000355994.7	c.51+15861G>T		intron_variant	Intron 2 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112170 AN: 152078 Hom.: 42853 Cov.: 34

Gnomad AFR AF: 0.514

Gnomad AMI AF: 0.857

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.810

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.752

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.737 AC: 112231 AN: 152194 Hom.: 42873 Cov.: 34 AF XY: 0.744 AC XY: 55340 AN XY: 74406

African (AFR) AF: 0.514 AC: 21314 AN: 41494

American (AMR) AF: 0.790 AC: 12093 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2974 AN: 3472

East Asian (EAS) AF: 0.856 AC: 4416 AN: 5158

South Asian (SAS) AF: 0.893 AC: 4310 AN: 4828

European-Finnish (FIN) AF: 0.866 AC: 9183 AN: 10610

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55330 AN: 68014

Other (OTH) AF: 0.755 AC: 1594 AN: 2110

Alfa AF: 0.763 Hom.: 17940

Bravo AF: 0.720

Asia WGS AF: 0.857 AC: 2982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.47
DANN	Benign	0.79
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1026520; hg19: chr18-74801306;