18-77021017-A-T

Variant names:

• chr18-77021017-A-T
• rs8096433
• NM_001025101.2:c.140-3749T>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.140-3749T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 152,174 control chromosomes in the GnomAD database, including 26,541 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 0.59 (26541 hom., cov: 34)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.140-3749T>A		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.140-3749T>A		intron_variant	Intron 3 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89197 AN: 152056 Hom.: 26504 Cov.: 34

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.582

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

GnomAD4 genome AF: 0.587 AC: 89299 AN: 152174 Hom.: 26541 Cov.: 34 AF XY: 0.587 AC XY: 43693 AN XY: 74404

African (AFR) AF: 0.640 AC: 26556 AN: 41500

American (AMR) AF: 0.609 AC: 9313 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1790 AN: 3470

East Asian (EAS) AF: 0.676 AC: 3507 AN: 5186

South Asian (SAS) AF: 0.629 AC: 3032 AN: 4824

European-Finnish (FIN) AF: 0.535 AC: 5661 AN: 10588

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.552 AC: 37538 AN: 68010

Other (OTH) AF: 0.586 AC: 1235 AN: 2108

Alfa AF: 0.574 Hom.: 3150

Bravo AF: 0.594

Asia WGS AF: 0.663 AC: 2304 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	0.80
DANN	Benign	0.24
PhyloP100		-0.48
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: rs8096433; hg19: chr18-74732973;