rs3794845

chr18-77002561-G-Cchr18-77002561-G-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBP	NM_001025101.2	c.577-12501C>G		intron_variant		ENST00000355994.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBP	ENST00000355994.7	c.577-12501C>G		intron_variant		5	NM_001025101.2	P1

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

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0968

Gnomad4 ASJ AF: 0.0899

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.106

Gnomad4 NFE AF: 0.0906

Gnomad4 OTH AF: 0.137

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.20
Dann	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs3794845; hg19: chr18-74714517;