chr18-77023179-G-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 65 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBP	NM_001025101.2	c.140-5911C>A		intron_variant	Intron 3 of 8	ENST00000355994.7	NP_001020272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBP	ENST00000355994.7	c.140-5911C>A		intron_variant	Intron 3 of 8	5	NM_001025101.2	ENSP00000348273.2

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

Gnomad4 AFR AF: 0.00616

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.0389

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.0272

Gnomad4 NFE AF: 0.0365

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0141 Hom.: 8

Bravo AF: 0.0199

Asia WGS AF: 0.00924 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.61
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11663697; hg19: chr18-74735135;