18-77022062-C-G

Variant names:

• chr18-77022062-C-G
• rs17660901
• NM_001025101.2:c.140-4794G>C

Variant summary

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

The NM_001025101.2(MBP):​c.140-4794G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,008 control chromosomes in the GnomAD database, including 6,699 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 0.27 (6699 hom., cov: 32)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.140-4794G>C		intron_variant	Intron 3 of 8	ENST00000355994.7	NP_001020272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBP	ENST00000355994.7	c.140-4794G>C		intron_variant	Intron 3 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40562 AN: 151890 Hom.: 6695 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.333

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.244

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.267 AC: 40567 AN: 152008 Hom.: 6699 Cov.: 32 AF XY: 0.267 AC XY: 19831 AN XY: 74306

African (AFR) AF: 0.0678 AC: 2811 AN: 41466

American (AMR) AF: 0.334 AC: 5101 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3470

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5172

South Asian (SAS) AF: 0.229 AC: 1099 AN: 4804

European-Finnish (FIN) AF: 0.352 AC: 3720 AN: 10560

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24440 AN: 67942

Other (OTH) AF: 0.275 AC: 580 AN: 2110

Alfa AF: 0.204 Hom.: 513

Bravo AF: 0.260

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		-0.16
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: rs17660901; hg19: chr18-74734018;