rs736421

Positions:

• chr18-77101609-G-A

Variant summary

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

The NM_001025101.2(MBP):​c.51+3602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,048 control chromosomes in the GnomAD database, including 9,127 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 0.31 (9127 hom., cov: 32)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBP	NM_001025101.2	c.51+3602C>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.51+3602C>T		intron_variant		5	NM_001025101.2	ENSP00000348273	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47396 AN: 151930 Hom.: 9130 Cov.: 32

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.310

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

GnomAD4 genome AF: 0.312 AC: 47395 AN: 152048 Hom.: 9127 Cov.: 32 AF XY: 0.318 AC XY: 23656 AN XY: 74310

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.310

Alfa AF: 0.383 Hom.: 16706

Bravo AF: 0.288

Asia WGS AF: 0.372 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.56
DANN	Benign	0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs736421; hg19: chr18-74813565;