18-77023179-G-T

Variant names:

• chr18-77023179-G-T
• rs11663697
• NM_001025101.2:c.140-5911C>A

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.140-5911C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0228 in 152,246 control chromosomes in the GnomAD database, including 65 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 0.023 (65 hom., cov: 33)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 6 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).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0228 (3475/152246) while in subpopulation NFE AF = 0.0365 (2482/68024). AF 95% confidence interval is 0.0353. There are 65 homozygotes in GnomAd4. There are 1607 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 65 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025101.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	NM_001025101.2	MANE Select	c.140-5911C>A		intron	N/A	NP_001020272.1
	MBP	NM_001025100.2		c.140-5911C>A		intron	N/A	NP_001020271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	ENST00000355994.7	TSL:5 MANE Select	c.140-5911C>A		intron	N/A	ENSP00000348273.2
	MBP	ENST00000397860.7	TSL:1	c.140-5911C>A		intron	N/A	ENSP00000380958.3
	MBP	ENST00000580402.5	TSL:5	c.140-5911C>A		intron	N/A	ENSP00000462223.1

Frequencies

GnomAD3 genomes AF: 0.0229 AC: 3479 AN: 152128 Hom.: 65 Cov.: 33

Gnomad AFR AF: 0.00618

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0139

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

GnomAD4 genome AF: 0.0228 AC: 3475 AN: 152246 Hom.: 65 Cov.: 33 AF XY: 0.0216 AC XY: 1607 AN XY: 74444

African (AFR) AF: 0.00616 AC: 256 AN: 41530

American (AMR) AF: 0.00804 AC: 123 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0300 AC: 145 AN: 4830

European-Finnish (FIN) AF: 0.0272 AC: 288 AN: 10602

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0365 AC: 2482 AN: 68024

Other (OTH) AF: 0.0137 AC: 29 AN: 2112

Alfa AF: 0.0156 Hom.: 15

Bravo AF: 0.0199

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.40
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs11663697; hg19: chr18-74735135;