18-77003697-G-T

Variant names:

• chr18-77003697-G-T
• rs2051344
• NM_001025101.2:c.576+13135C>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.576+13135C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,082 control chromosomes in the GnomAD database, including 6,886 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 0.27 (6886 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 14 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]

ENSG00000279811 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025101.2. 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.576+13135C>A		intron	N/A	NP_001020272.1
	MBP	NM_001025081.2		c.255+6152C>A		intron	N/A	NP_001020252.1
	MBP	NM_002385.3		c.255+6152C>A		intron	N/A	NP_002376.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	ENST00000355994.7	TSL:5 MANE Select	c.576+13135C>A		intron	N/A	ENSP00000348273.2
	MBP	ENST00000382582.7	TSL:1	c.255+6152C>A		intron	N/A	ENSP00000372025.3
	MBP	ENST00000359645.7	TSL:1	c.255+6152C>A		intron	N/A	ENSP00000352667.3

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40933 AN: 151964 Hom.: 6884 Cov.: 33

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.276

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.269 AC: 40937 AN: 152082 Hom.: 6886 Cov.: 33 AF XY: 0.272 AC XY: 20226 AN XY: 74342

African (AFR) AF: 0.0697 AC: 2895 AN: 41524

American (AMR) AF: 0.404 AC: 6166 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1004 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1308 AN: 5176

South Asian (SAS) AF: 0.231 AC: 1116 AN: 4822

European-Finnish (FIN) AF: 0.371 AC: 3920 AN: 10552

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23537 AN: 67952

Other (OTH) AF: 0.275 AC: 580 AN: 2112

Alfa AF: 0.314 Hom.: 25109

Bravo AF: 0.263

Asia WGS AF: 0.266 AC: 923 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.045
DANN	Benign	0.36
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2051344; hg19: chr18-74715653;