18-77002561-G-C

Variant names:

• chr18-77002561-G-C
• rs3794845
• NM_001025101.2:c.577-12501C>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.577-12501C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 141,262 control chromosomes in the GnomAD database, including 1,105 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 0.12 (1105 hom., cov: 32)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 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.577-12501C>G		intron	N/A	NP_001020272.1
	MBP	NM_001025081.2		c.255+7288C>G		intron	N/A	NP_001020252.1
	MBP	NM_002385.3		c.255+7288C>G		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.577-12501C>G		intron	N/A	ENSP00000348273.2
	MBP	ENST00000382582.7	TSL:1	c.255+7288C>G		intron	N/A	ENSP00000372025.3
	MBP	ENST00000359645.7	TSL:1	c.255+7288C>G		intron	N/A	ENSP00000352667.3

Frequencies

GnomAD3 genomes AF: 0.122 AC: 17266 AN: 141140 Hom.: 1101 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0727

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0906

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.122 AC: 17288 AN: 141262 Hom.: 1105 Cov.: 32 AF XY: 0.124 AC XY: 8544 AN XY: 69046

African (AFR) AF: 0.182 AC: 7244 AN: 39766

American (AMR) AF: 0.0968 AC: 1371 AN: 14170

Ashkenazi Jewish (ASJ) AF: 0.0899 AC: 284 AN: 3158

East Asian (EAS) AF: 0.115 AC: 561 AN: 4864

South Asian (SAS) AF: 0.179 AC: 819 AN: 4582

European-Finnish (FIN) AF: 0.106 AC: 1030 AN: 9732

Middle Eastern (MID) AF: 0.149 AC: 40 AN: 268

European-Non Finnish (NFE) AF: 0.0906 AC: 5611 AN: 61914

Other (OTH) AF: 0.137 AC: 264 AN: 1928

Alfa AF: 0.0403 Hom.: 35

Bravo AF: 0.116

Asia WGS AF: 0.144 AC: 479 AN: 3330

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.40
PhyloP100		-0.57
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: rs3794845; hg19: chr18-74714517;