rs12967023

Positions:

• chr18-77008428-G-A
• chr18-77008428-G-C

Variant summary

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

The NM_001025101.2(MBP):​c.576+8404C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 152,078 control chromosomes in the GnomAD database, including 4,656 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 0.23 (4656 hom., cov: 32)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0260

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBP	NM_001025101.2	c.576+8404C>T		intron_variant		ENST00000355994.7	NP_001020272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBP	ENST00000355994.7	c.576+8404C>T		intron_variant		5	NM_001025101.2	ENSP00000348273	P1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34585 AN: 151962 Hom.: 4659 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.0819

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.227 AC: 34581 AN: 152078 Hom.: 4656 Cov.: 32 AF XY: 0.222 AC XY: 16495 AN XY: 74342

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.0821

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.254

Alfa AF: 0.287 Hom.: 6429

Bravo AF: 0.223

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.47

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: rs12967023; hg19: chr18-74720384; COSMIC: COSV62830082; COSMIC: COSV62830082;