18-77005659-G-T

Position:

• chr18-77005659-G-T

Variant summary

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

The NM_001025101.2(MBP):​c.576+11173C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,236 control chromosomes in the GnomAD database, including 44,294 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 0.76 (44258 hom., cov: 32)
  • Exomes 𝑓: 0.77 (36 hom.)
• 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBP	NM_001025101.2	c.576+11173C>A		intron_variant		ENST00000355994.7	NP_001020272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBP	ENST00000355994.7	c.576+11173C>A		intron_variant		5	NM_001025101.2	ENSP00000348273	P1
	ENST00000624814.1	n.1188C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115672 AN: 152006 Hom.: 44233 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.753

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.772 AC: 88 AN: 114 Hom.: 36 Cov.: 0 AF XY: 0.782 AC XY: 61 AN XY: 78

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.750

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.821

Gnomad4 OTH exome AF: 0.400

GnomAD4 genome AF: 0.761 AC: 115750 AN: 152122 Hom.: 44258 Cov.: 32 AF XY: 0.759 AC XY: 56456 AN XY: 74370

Gnomad4 AFR AF: 0.775

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.778

Gnomad4 EAS AF: 0.534

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.772

Gnomad4 OTH AF: 0.756

Alfa AF: 0.768 Hom.: 93407

Bravo AF: 0.763

Asia WGS AF: 0.581 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.36
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs509620; hg19: chr18-74717615;