rs3794832

Variant names:

• chr18-77010747-G-A
• rs3794832
• NM_001025101.2:c.576+6085C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001025101.2(MBP):​c.576+6085C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0289 in 152,286 control chromosomes in the GnomAD database, including 82 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 0.029 (82 hom., cov: 33)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• Publications: 3 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=-0.87).
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0289 (4395/152286) while in subpopulation AMR AF = 0.0468 (716/15292). AF 95% confidence interval is 0.044. There are 82 homozygotes in GnomAd4. There are 2321 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 82 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.576+6085C>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+6085C>T		intron_variant	Intron 4 of 8	5	NM_001025101.2	ENSP00000348273.2

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4389 AN: 152168 Hom.: 81 Cov.: 33

Gnomad AFR AF: 0.00714

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0468

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.0406

Gnomad SAS AF: 0.0383

Gnomad FIN AF: 0.0490

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0320

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0289 AC: 4395 AN: 152286 Hom.: 82 Cov.: 33 AF XY: 0.0312 AC XY: 2321 AN XY: 74470

African (AFR) AF: 0.00712 AC: 296 AN: 41554

American (AMR) AF: 0.0468 AC: 716 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 180 AN: 3472

East Asian (EAS) AF: 0.0405 AC: 210 AN: 5182

South Asian (SAS) AF: 0.0381 AC: 184 AN: 4826

European-Finnish (FIN) AF: 0.0490 AC: 520 AN: 10614

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0320 AC: 2176 AN: 68026

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0293 Hom.: 68

Bravo AF: 0.0270

Asia WGS AF: 0.0470 AC: 163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.54
PhyloP100		0.013
Mutation Taster		=100/0	polymorphism

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: rs3794832; hg19: chr18-74722703;