rs535878

Variant names:

• chr3-39494393-A-G
• rs535878
• NM_001393704.1:c.-4-7673A>G

Variant summary

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

The NM_001393704.1(MOBP):​c.-4-7673A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 151,612 control chromosomes in the GnomAD database, including 13,265 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 0.36 (13265 hom., cov: 32)
• Consequence: MOBP NM_001393704.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 4 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 = 0.696 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.-4-7673A>G		intron	N/A	NP_001380633.1
	MOBP	NM_001278322.2		c.-4-7673A>G		intron	N/A	NP_001265251.1
	MOBP	NM_001278323.2		c.-4-7673A>G		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.-4-7673A>G		intron	N/A	ENSP00000508923.1
	MOBP	ENST00000383754.7	TSL:1	c.-4-7673A>G		intron	N/A	ENSP00000373261.3
	MOBP	ENST00000452959.6	TSL:1	n.-4-7673A>G		intron	N/A	ENSP00000405549.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 53918 AN: 151500 Hom.: 13225 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.356 AC: 54010 AN: 151612 Hom.: 13265 Cov.: 32 AF XY: 0.350 AC XY: 25896 AN XY: 74092

African (AFR) AF: 0.702 AC: 28983 AN: 41260

American (AMR) AF: 0.228 AC: 3487 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 965 AN: 3462

East Asian (EAS) AF: 0.275 AC: 1416 AN: 5154

South Asian (SAS) AF: 0.320 AC: 1542 AN: 4812

European-Finnish (FIN) AF: 0.174 AC: 1823 AN: 10490

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.219 AC: 14842 AN: 67852

Other (OTH) AF: 0.329 AC: 694 AN: 2112

Alfa AF: 0.265 Hom.: 21426

Bravo AF: 0.375

Asia WGS AF: 0.337 AC: 1171 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	7.1
DANN	Benign	0.77
PhyloP100		1.0
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: rs535878; hg19: chr3-39535884;