chr4-165333201-C-G

Position:

• chr4-165333201-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006745.5(MSMO1):​c.-31-139C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 590,456 control chromosomes in the GnomAD database, including 106,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (23650 hom., cov: 33)
  • Exomes 𝑓: 0.60 (82469 hom.)
• Consequence: MSMO1 NM_006745.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.487

Genes affected

MSMO1 (HGNC:10545): (methylsterol monooxygenase 1) Sterol-C4-mehtyl oxidase-like protein was isolated based on its similarity to the yeast ERG25 protein. It contains a set of putative metal binding motifs with similarity to that seen in a family of membrane desaturases-hydroxylases. The protein is localized to the endoplasmic reticulum membrane and is believed to function in cholesterol biosynthesis. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-165333201-C-G is Benign according to our data. Variant chr4-165333201-C-G is described in ClinVar as [Benign]. Clinvar id is 1270307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MSMO1	NM_006745.5	c.-31-139C>G		intron_variant		ENST00000261507.11	NP_006736.1
MSMO1	NM_001017369.3	c.-138-4588C>G		intron_variant			NP_001017369.1
MSMO1	XM_005263176.3	c.-31-139C>G		intron_variant			XP_005263233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MSMO1	ENST00000261507.11	c.-31-139C>G		intron_variant		1	NM_006745.5	ENSP00000261507	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81043 AN: 151946 Hom.: 23637 Cov.: 33

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.605 AC: 265065 AN: 438390 Hom.: 82469 AF XY: 0.606 AC XY: 137660 AN XY: 227272

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.658

Gnomad4 ASJ exome AF: 0.530

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.641

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.533 AC: 81077 AN: 152066 Hom.: 23650 Cov.: 33 AF XY: 0.538 AC XY: 40015 AN XY: 74328

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.529

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.554

Alfa AF: 0.439 Hom.: 1314

Bravo AF: 0.521

Asia WGS AF: 0.524 AC: 1812 AN: 3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.72

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: rs3775318; hg19: chr4-166254353;