18-77020516-G-T

Variant names:

• chr18-77020516-G-T
• rs921336
• NM_001025101.2:c.140-3248C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001025101.2(MBP):​c.140-3248C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,082 control chromosomes in the GnomAD database, including 3,821 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 0.21 (3821 hom., cov: 32)
• Consequence: MBP NM_001025101.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	NM_001025101.2	MANE Select	c.140-3248C>A		intron	N/A	NP_001020272.1	P02686-1
	MBP	NM_001025100.2		c.140-3248C>A		intron	N/A	NP_001020271.1	P02686-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBP	ENST00000355994.7	TSL:5 MANE Select	c.140-3248C>A		intron	N/A	ENSP00000348273.2	P02686-1
	MBP	ENST00000397860.7	TSL:1	c.140-3248C>A		intron	N/A	ENSP00000380958.3	P02686-2
	MBP	ENST00000580402.5	TSL:5	c.140-3248C>A		intron	N/A	ENSP00000462223.1	P02686-1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31505 AN: 151964 Hom.: 3806 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.208 AC: 31559 AN: 152082 Hom.: 3821 Cov.: 32 AF XY: 0.211 AC XY: 15718 AN XY: 74354

African (AFR) AF: 0.311 AC: 12896 AN: 41436

American (AMR) AF: 0.191 AC: 2928 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1849 AN: 5156

South Asian (SAS) AF: 0.314 AC: 1516 AN: 4824

European-Finnish (FIN) AF: 0.158 AC: 1677 AN: 10604

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.142 AC: 9664 AN: 67982

Other (OTH) AF: 0.211 AC: 446 AN: 2114

Alfa AF: 0.159 Hom.: 3515

Bravo AF: 0.211

Asia WGS AF: 0.334 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.57
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs921336;

hg19: chr18-74732472;