rs2233204

Positions:

• chr3-39513295-C-T

Variant summary

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

The NM_001278322.2(MOBP):​c.621-88C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,247,652 control chromosomes in the GnomAD database, including 70,728 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 0.26 (6200 hom., cov: 33)
  • Exomes 𝑓: 0.34 (64528 hom.)
• Consequence: MOBP NM_001278322.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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]

MOBP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.352 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOBP	NM_001278322.2	c.621-88C>T		intron_variant			NP_001265251.1
MOBP	NM_182935.4	c.207-88C>T		intron_variant			NP_891980.1
MOBP	NR_003090.3	n.356-88C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOBP	ENST00000383754.7	c.207-88C>T		intron_variant		1		ENSP00000373261.3
MOBP	ENST00000424090.5	n.*35-88C>T		intron_variant		1		ENSP00000389055.1
MOBP	ENST00000442631.5	n.549-88C>T		intron_variant		1		ENSP00000413771.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39060 AN: 152010 Hom.: 6200 Cov.: 33

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0824

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.335 AC: 367401 AN: 1095524 Hom.: 64528 AF XY: 0.335 AC XY: 185781 AN XY: 555094

Gnomad4 AFR exome AF: 0.0847

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.374

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.257 AC: 39048 AN: 152128 Hom.: 6200 Cov.: 33 AF XY: 0.258 AC XY: 19151 AN XY: 74360

Gnomad4 AFR AF: 0.0917

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.0832

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.249

Alfa AF: 0.325 Hom.: 6446

Bravo AF: 0.237

Asia WGS AF: 0.136 AC: 476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.85
DANN	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2233204; hg19: chr3-39554786;