rs864643

Positions:

• chr3-39514089-A-G
• chr3-39514089-A-T

Variant summary

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

The ENST00000383754.7(MOBP):​c.*667A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,028 control chromosomes in the GnomAD database, including 10,019 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 0.32 (10019 hom., cov: 31)
  • Exomes 𝑓: 0.15 (0 hom.)
• Consequence: MOBP ENST00000383754.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0160

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MOBP	NM_001278322.2	c.*706A>G		3_prime_UTR_variant	5/5		NP_001265251.1
MOBP	NM_182935.4	c.*667A>G		3_prime_UTR_variant	4/4		NP_891980.1
MOBP	NR_103506.2	n.852A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MOBP	ENST00000383754.7	c.*667A>G		3_prime_UTR_variant	4/4	1		ENSP00000373261	P1
MOBP	ENST00000424090.5	c.*258+483A>G		intron_variant, NMD_transcript_variant		1		ENSP00000389055
MOBP	ENST00000442631.5	c.*223+483A>G		intron_variant, NMD_transcript_variant		1		ENSP00000413771

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47893 AN: 151844 Hom.: 9990 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.147 AC: 10 AN: 68 Hom.: 0 Cov.: 0 AF XY: 0.146 AC XY: 7 AN XY: 48

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.154

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.316 AC: 47984 AN: 151960 Hom.: 10019 Cov.: 31 AF XY: 0.311 AC XY: 23073 AN XY: 74294

Gnomad4 AFR AF: 0.601

Gnomad4 AMR AF: 0.263

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.140

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.288

Alfa AF: 0.220 Hom.: 5939

Bravo AF: 0.335

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.59

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: rs864643; hg19: chr3-39555580;