rs12967023

Variant names:

• chr18-77008428-G-A
• rs12967023
• NM_001025101.2:c.576+8404C>T

Your query was ambiguous. Multiple possible variants found:

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

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+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
• 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=-0.9).
• 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 rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.576+8404C>T		intron_variant	Intron 4 of 8	ENST00000355994.7	NP_001020272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBP	ENST00000355994.7	c.576+8404C>T		intron_variant	Intron 4 of 8	5	NM_001025101.2	ENSP00000348273.2

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

African (AFR) AF: 0.105 AC: 4367 AN: 41482

American (AMR) AF: 0.229 AC: 3502 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3468

East Asian (EAS) AF: 0.0821 AC: 424 AN: 5162

South Asian (SAS) AF: 0.189 AC: 907 AN: 4810

European-Finnish (FIN) AF: 0.227 AC: 2401 AN: 10598

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21134 AN: 67958

Other (OTH) AF: 0.254 AC: 536 AN: 2108

Alfa AF: 0.280 Hom.: 8125

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
PhyloP100		0.026
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: rs12967023; hg19: chr18-74720384; COSMIC: COSV62830082; COSMIC: COSV62830082;