rs2000811

Variant names:

• chr18-77097372-C-T
• rs2000811
• NM_001025101.2:c.51+7839G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025101.2(MBP):​c.51+7839G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,154 control chromosomes in the GnomAD database, including 10,176 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 0.34 (10172 hom., cov: 33)
  • Exomes 𝑓: 0.41 (4 hom.)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.51+7839G>A		intron_variant	Intron 2 of 8	ENST00000355994.7	NP_001020272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBP	ENST00000355994.7	c.51+7839G>A		intron_variant	Intron 2 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52065 AN: 151978 Hom.: 10178 Cov.: 33

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.349

GnomAD4 exome AF: 0.411 AC: 23 AN: 56 Hom.: 4 Cov.: 0 AF XY: 0.406 AC XY: 13 AN XY: 32

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.472

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.342 AC: 52078 AN: 152098 Hom.: 10172 Cov.: 33 AF XY: 0.349 AC XY: 25978 AN XY: 74338

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.408

Gnomad4 SAS AF: 0.598

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.347

Alfa AF: 0.403 Hom.: 16759

Bravo AF: 0.319

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.44

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2000811; hg19: chr18-74809328;