rs10514234

Variant names:

• chr18-77003793-T-C
• rs10514234
• NM_001025101.2:c.576+13039A>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.576+13039A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 152,270 control chromosomes in the GnomAD database, including 265 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 0.056 (265 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: -0.295
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.576+13039A>G		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+13039A>G		intron_variant	Intron 4 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.0555 AC: 8451 AN: 152154 Hom.: 261 Cov.: 33

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0305

Gnomad EAS AF: 0.0727

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0483

Gnomad MID AF: 0.0929

Gnomad NFE AF: 0.0488

Gnomad OTH AF: 0.0690

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

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

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0556 AC: 8473 AN: 152270 Hom.: 265 Cov.: 33 AF XY: 0.0558 AC XY: 4151 AN XY: 74442

African (AFR) AF: 0.0645 AC: 2680 AN: 41562

American (AMR) AF: 0.0420 AC: 642 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0305 AC: 106 AN: 3470

East Asian (EAS) AF: 0.0725 AC: 376 AN: 5184

South Asian (SAS) AF: 0.128 AC: 616 AN: 4818

European-Finnish (FIN) AF: 0.0483 AC: 513 AN: 10618

Middle Eastern (MID) AF: 0.0931 AC: 27 AN: 290

European-Non Finnish (NFE) AF: 0.0488 AC: 3318 AN: 68012

Other (OTH) AF: 0.0740 AC: 156 AN: 2108

Alfa AF: 0.0533 Hom.: 156

Bravo AF: 0.0547

Asia WGS AF: 0.0930 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.55
PhyloP100		-0.29
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: rs10514234; hg19: chr18-74715749;