rs12458282

Variant names:

• chr18-77061897-T-C
• rs12458282
• NM_001025101.2:c.139+4401A>G

Variant summary

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

The NM_001025101.2(MBP):​c.139+4401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,220 control chromosomes in the GnomAD database, including 5,112 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 0.25 (5112 hom., cov: 33)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 4 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 = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.139+4401A>G		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.139+4401A>G		intron_variant	Intron 3 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37629 AN: 152102 Hom.: 5107 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.247 AC: 37658 AN: 152220 Hom.: 5112 Cov.: 33 AF XY: 0.246 AC XY: 18286 AN XY: 74430

African (AFR) AF: 0.138 AC: 5749 AN: 41554

American (AMR) AF: 0.267 AC: 4088 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 973 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1455 AN: 5178

South Asian (SAS) AF: 0.275 AC: 1326 AN: 4824

European-Finnish (FIN) AF: 0.304 AC: 3222 AN: 10584

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20065 AN: 68002

Other (OTH) AF: 0.265 AC: 559 AN: 2112

Alfa AF: 0.269 Hom.: 1532

Bravo AF: 0.240

Asia WGS AF: 0.272 AC: 944 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	0.019
DANN	Benign	0.43
PhyloP100		-2.0
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: rs12458282; hg19: chr18-74773853;