rs2000811

Variant names:

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

Variant summary

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

The ENST00000355994.7(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 ENST00000355994.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000355994.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	NM_001025101.2	MANE Select	c.51+7839G>A		intron	N/A	NP_001020272.1
	MBP	NM_001025100.2		c.51+7839G>A		intron	N/A	NP_001020271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	ENST00000355994.7	TSL:5 MANE Select	c.51+7839G>A		intron	N/A	ENSP00000348273.2
	MBP	ENST00000397860.7	TSL:1	c.51+7839G>A		intron	N/A	ENSP00000380958.3
	MBP	ENST00000487778.5	TSL:3	n.414G>A		non_coding_transcript_exon	Exon 3 of 5

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

African (AFR) AF: 0.167 AC: 1 AN: 6

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 4 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.472 AC: 17 AN: 36

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.157 AC: 6510 AN: 41514

American (AMR) AF: 0.340 AC: 5206 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1420 AN: 3472

East Asian (EAS) AF: 0.408 AC: 2105 AN: 5160

South Asian (SAS) AF: 0.598 AC: 2890 AN: 4830

European-Finnish (FIN) AF: 0.456 AC: 4818 AN: 10564

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28060 AN: 67952

Other (OTH) AF: 0.347 AC: 732 AN: 2112

Alfa AF: 0.387 Hom.: 35620

Bravo AF: 0.319

Asia WGS AF: 0.450 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.47
DANN	Benign	0.44
PhyloP100		-0.71
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: rs2000811; hg19: chr18-74809328;