18-77026349-A-G

Variant names:

• chr18-77026349-A-G
• rs2282574
• NM_001025101.2:c.140-9081T>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.140-9081T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.681 in 152,168 control chromosomes in the GnomAD database, including 35,456 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 0.68 (35456 hom., cov: 33)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.576
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.140-9081T>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.140-9081T>C		intron_variant	Intron 3 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103478 AN: 152048 Hom.: 35437 Cov.: 33

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.681 AC: 103553 AN: 152168 Hom.: 35456 Cov.: 33 AF XY: 0.683 AC XY: 50823 AN XY: 74390

African (AFR) AF: 0.710 AC: 29468 AN: 41512

American (AMR) AF: 0.699 AC: 10691 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2122 AN: 3472

East Asian (EAS) AF: 0.805 AC: 4164 AN: 5170

South Asian (SAS) AF: 0.649 AC: 3131 AN: 4826

European-Finnish (FIN) AF: 0.677 AC: 7151 AN: 10566

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.656 AC: 44597 AN: 68002

Other (OTH) AF: 0.675 AC: 1427 AN: 2114

Alfa AF: 0.669 Hom.: 9093

Bravo AF: 0.685

Asia WGS AF: 0.714 AC: 2482 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.75
DANN	Benign	0.25
PhyloP100		-0.58
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: rs2282574; hg19: chr18-74738305;