rs2008323

Variant names:

• chr18-77061980-T-C
• rs2008323
• NM_001025101.2:c.139+4318A>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+4318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,072 control chromosomes in the GnomAD database, including 19,715 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 0.47 (19715 hom., cov: 33)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.89
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.139+4318A>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+4318A>G		intron_variant	Intron 3 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71651 AN: 151954 Hom.: 19673 Cov.: 33

Gnomad AFR AF: 0.769

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.437

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

GnomAD4 genome AF: 0.472 AC: 71748 AN: 152072 Hom.: 19715 Cov.: 33 AF XY: 0.465 AC XY: 34587 AN XY: 74330

African (AFR) AF: 0.769 AC: 31925 AN: 41494

American (AMR) AF: 0.373 AC: 5704 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1869 AN: 5174

South Asian (SAS) AF: 0.368 AC: 1772 AN: 4818

European-Finnish (FIN) AF: 0.342 AC: 3617 AN: 10564

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24112 AN: 67952

Other (OTH) AF: 0.438 AC: 926 AN: 2114

Alfa AF: 0.385 Hom.: 23592

Bravo AF: 0.490

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.017
DANN	Benign	0.25
PhyloP100		-4.9
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: rs2008323; hg19: chr18-74773936;