rs736421

Variant names:

• chr18-77101609-G-A
• rs736421
• NM_001025101.2:c.51+3602C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.96).
• 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 rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.51+3602C>T		intron_variant	Intron 2 of 8	ENST00000355994.7	NP_001020272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBP	ENST00000355994.7	c.51+3602C>T		intron_variant	Intron 2 of 8	5	NM_001025101.2	ENSP00000348273.2

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

African (AFR) AF: 0.0841 AC: 3491 AN: 41514

American (AMR) AF: 0.343 AC: 5240 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3472

East Asian (EAS) AF: 0.372 AC: 1922 AN: 5164

South Asian (SAS) AF: 0.486 AC: 2344 AN: 4822

European-Finnish (FIN) AF: 0.424 AC: 4474 AN: 10548

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27742 AN: 67944

Other (OTH) AF: 0.310 AC: 654 AN: 2110

Alfa AF: 0.371 Hom.: 21528

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs736421; hg19: chr18-74813565;