rs538867

Variant names:

• chr3-39471787-C-T
• rs538867
• NM_001393704.1:c.-89+4047C>T

Variant summary

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

The NM_001393704.1(MOBP):​c.-89+4047C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 152,202 control chromosomes in the GnomAD database, including 1,151 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 0.093 (1151 hom., cov: 32)
• Consequence: MOBP NM_001393704.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 14 publications found

Genes affected

MOBP (HGNC:7189): (myelin associated oligodendrocyte basic protein) Predicted to enable actin binding activity and myosin binding activity. Predicted to be a structural constituent of myelin sheath. Predicted to be involved in nervous system development. Predicted to be located in mitochondrion. Predicted to be active in cortical actin cytoskeleton. Implicated in frontotemporal dementia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393704.1. 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
	MOBP	NM_001393704.1	MANE Select	c.-89+4047C>T		intron	N/A	NP_001380633.1
	MOBP	NM_001278322.2		c.-89+4047C>T		intron	N/A	NP_001265251.1
	MOBP	NM_001278323.2		c.-5+4047C>T		intron	N/A	NP_001265252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOBP	ENST00000684792.1	MANE Select	c.-89+4047C>T		intron	N/A	ENSP00000508923.1
	MOBP	ENST00000383754.7	TSL:1	c.-89+4047C>T		intron	N/A	ENSP00000373261.3
	MOBP	ENST00000452959.6	TSL:1	n.-89+4047C>T		intron	N/A	ENSP00000405549.1

Frequencies

GnomAD3 genomes AF: 0.0933 AC: 14185 AN: 152084 Hom.: 1144 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0406

Gnomad OTH AF: 0.0836

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

GnomAD4 genome AF: 0.0934 AC: 14217 AN: 152202 Hom.: 1151 Cov.: 32 AF XY: 0.0909 AC XY: 6767 AN XY: 74416

African (AFR) AF: 0.213 AC: 8829 AN: 41486

American (AMR) AF: 0.0431 AC: 659 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 297 AN: 3472

East Asian (EAS) AF: 0.162 AC: 838 AN: 5170

South Asian (SAS) AF: 0.0623 AC: 300 AN: 4818

European-Finnish (FIN) AF: 0.0314 AC: 333 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0406 AC: 2764 AN: 68026

Other (OTH) AF: 0.0822 AC: 174 AN: 2116

Alfa AF: 0.0690 Hom.: 1393

Bravo AF: 0.0993

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.6
DANN	Benign	0.58
PhyloP100		0.029
Mutation Taster		=100/0	polymorphism (auto)

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: rs538867; hg19: chr3-39513278;