18-77095185-C-T

Variant names:

• chr18-77095185-C-T
• rs2282566
• NM_001025101.2:c.51+10026G>A

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+10026G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,088 control chromosomes in the GnomAD database, including 9,938 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 0.33 (9938 hom., cov: 33)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.458 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	NM_001025101.2	MANE Select	c.51+10026G>A		intron	N/A	NP_001020272.1	P02686-1
	MBP	NM_001025100.2		c.51+10026G>A		intron	N/A	NP_001020271.1	P02686-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	ENST00000355994.7	TSL:5 MANE Select	c.51+10026G>A		intron	N/A	ENSP00000348273.2	P02686-1
	MBP	ENST00000397860.7	TSL:1	c.51+10026G>A		intron	N/A	ENSP00000380958.3	P02686-2
	MBP	ENST00000580402.5	TSL:5	c.51+10026G>A		intron	N/A	ENSP00000462223.1	P02686-1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50474 AN: 151970 Hom.: 9937 Cov.: 33

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.332 AC: 50491 AN: 152088 Hom.: 9938 Cov.: 33 AF XY: 0.339 AC XY: 25201 AN XY: 74326

African (AFR) AF: 0.116 AC: 4807 AN: 41508

American (AMR) AF: 0.346 AC: 5285 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1665 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1996 AN: 5172

South Asian (SAS) AF: 0.475 AC: 2288 AN: 4820

European-Finnish (FIN) AF: 0.492 AC: 5196 AN: 10564

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28012 AN: 67970

Other (OTH) AF: 0.344 AC: 726 AN: 2112

Alfa AF: 0.394 Hom.: 20853

Bravo AF: 0.311

Asia WGS AF: 0.392 AC: 1364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.34
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2282566;

hg19: chr18-74807141;