11-3088178-C-T

Variant names:

• chr11-3088178-C-T
• rs2289998
• NM_020896.4:c.*27G>A

Variant summary

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

The NM_020896.4(OSBPL5):​c.*27G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,527,110 control chromosomes in the GnomAD database, including 384,217 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 0.72 (39003 hom., cov: 33)
  • Exomes 𝑓: 0.71 (345214 hom.)
• Consequence: OSBPL5 NM_020896.4 3_prime_UTR
• Scores: Splicing: ADA: 0.00006899
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 14 publications found

Genes affected

OSBPL5 (HGNC:16392): (oxysterol binding protein like 5) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors that play a key role in the maintenance of cholesterol balance in the body. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. This gene has been shown to be imprinted, with preferential expression from the maternal allele only in placenta. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020896.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL5	NM_020896.4	MANE Select	c.*27G>A		3_prime_UTR	Exon 22 of 22	NP_065947.1	Q9H0X9-1
	OSBPL5	NM_001144063.2		c.*27G>A		3_prime_UTR	Exon 21 of 21	NP_001137535.1	Q9H0X9-2
	OSBPL5	NM_145638.3		c.*27G>A		3_prime_UTR	Exon 21 of 21	NP_663613.1	Q9H0X9-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL5	ENST00000263650.12	TSL:1 MANE Select	c.*27G>A		3_prime_UTR	Exon 22 of 22	ENSP00000263650.7	Q9H0X9-1
	OSBPL5	ENST00000389989.7	TSL:1	c.*27G>A		3_prime_UTR	Exon 21 of 21	ENSP00000374639.3	Q9H0X9-2
	OSBPL5	ENST00000534454.5	TSL:5	c.*27G>A		splice_region	Exon 11 of 12	ENSP00000431412.1	H0YCD7

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108550 AN: 151618 Hom.: 38957 Cov.: 33

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.838

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.684

GnomAD2 exomes AF: 0.715 AC: 135028 AN: 188864 AF XY: 0.717

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.731

Gnomad ASJ exome AF: 0.650

Gnomad EAS exome AF: 0.810

Gnomad FIN exome AF: 0.684

Gnomad NFE exome AF: 0.679

Gnomad OTH exome AF: 0.665

GnomAD4 exome AF: 0.706 AC: 971686 AN: 1375374 Hom.: 345214 Cov.: 31 AF XY: 0.710 AC XY: 480440 AN XY: 676586

African (AFR) AF: 0.744 AC: 22892 AN: 30776

American (AMR) AF: 0.728 AC: 26042 AN: 35774

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 14682 AN: 22224

East Asian (EAS) AF: 0.842 AC: 30717 AN: 36484

South Asian (SAS) AF: 0.833 AC: 61488 AN: 73800

European-Finnish (FIN) AF: 0.696 AC: 34684 AN: 49848

Middle Eastern (MID) AF: 0.726 AC: 3888 AN: 5352

European-Non Finnish (NFE) AF: 0.693 AC: 737661 AN: 1064490

Other (OTH) AF: 0.700 AC: 39632 AN: 56626

GnomAD4 genome AF: 0.716 AC: 108652 AN: 151736 Hom.: 39003 Cov.: 33 AF XY: 0.721 AC XY: 53493 AN XY: 74160

African (AFR) AF: 0.746 AC: 30888 AN: 41428

American (AMR) AF: 0.708 AC: 10810 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.678 AC: 2351 AN: 3468

East Asian (EAS) AF: 0.816 AC: 4189 AN: 5134

South Asian (SAS) AF: 0.838 AC: 4041 AN: 4820

European-Finnish (FIN) AF: 0.697 AC: 7328 AN: 10516

Middle Eastern (MID) AF: 0.741 AC: 215 AN: 290

European-Non Finnish (NFE) AF: 0.689 AC: 46681 AN: 67800

Other (OTH) AF: 0.687 AC: 1450 AN: 2110

Alfa AF: 0.643 Hom.: 4000

Bravo AF: 0.714

Asia WGS AF: 0.824 AC: 2866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.7
DANN	Benign	0.67
PhyloP100		-0.014
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000069
dbscSNV1_RF	Benign	0.0060
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: rs2289998; hg19: chr11-3109408; COSMIC: COSV55141855; COSMIC: COSV55141855;