3-31748090-T-C

Variant names:

• chr3-31748090-T-C
• rs2290532
• NM_017784.5:c.760A>G

Variant summary

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

The NM_017784.5(OSBPL10):​c.760A>G​(p.Asn254Asp) variant causes a missense change. The variant allele was found at a frequency of 0.453 in 1,612,980 control chromosomes in the GnomAD database, including 174,263 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (13219 hom., cov: 32)
  • Exomes 𝑓: 0.46 (161044 hom.)
• Consequence: OSBPL10 NM_017784.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.94
• Publications: 34 publications found

Genes affected

OSBPL10 (HGNC:16395): (oxysterol binding protein like 10) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Like most members, the encoded protein contains an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=5.621795E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.736 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL10	NM_017784.5	c.760A>G	p.Asn254Asp	missense_variant	Exon 5 of 12	ENST00000396556.7	NP_060254.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL10	ENST00000396556.7	c.760A>G	p.Asn254Asp	missense_variant	Exon 5 of 12	1	NM_017784.5	ENSP00000379804.2

Frequencies

GnomAD3 genomes AF: 0.375 AC: 57006 AN: 151932 Hom.: 13220 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.756

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.470

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.378

GnomAD2 exomes AF: 0.481 AC: 120098 AN: 249498 AF XY: 0.479

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.665

Gnomad ASJ exome AF: 0.398

Gnomad EAS exome AF: 0.755

Gnomad FIN exome AF: 0.475

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.437

GnomAD4 exome AF: 0.461 AC: 672890 AN: 1460930 Hom.: 161044 Cov.: 54 AF XY: 0.461 AC XY: 335224 AN XY: 726690

African (AFR) AF: 0.0902 AC: 3020 AN: 33476

American (AMR) AF: 0.647 AC: 28845 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 10399 AN: 26126

East Asian (EAS) AF: 0.767 AC: 30435 AN: 39674

South Asian (SAS) AF: 0.496 AC: 42797 AN: 86214

European-Finnish (FIN) AF: 0.480 AC: 25597 AN: 53350

Middle Eastern (MID) AF: 0.338 AC: 1948 AN: 5760

European-Non Finnish (NFE) AF: 0.453 AC: 503452 AN: 1111366

Other (OTH) AF: 0.437 AC: 26397 AN: 60350

GnomAD4 genome AF: 0.375 AC: 56998 AN: 152050 Hom.: 13219 Cov.: 32 AF XY: 0.382 AC XY: 28349 AN XY: 74304

African (AFR) AF: 0.107 AC: 4428 AN: 41508

American (AMR) AF: 0.531 AC: 8119 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3472

East Asian (EAS) AF: 0.756 AC: 3895 AN: 5150

South Asian (SAS) AF: 0.509 AC: 2453 AN: 4820

European-Finnish (FIN) AF: 0.470 AC: 4970 AN: 10566

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30423 AN: 67936

Other (OTH) AF: 0.376 AC: 794 AN: 2110

Alfa AF: 0.422 Hom.: 47882

Bravo AF: 0.368

TwinsUK AF: 0.463 AC: 1716

ALSPAC AF: 0.469 AC: 1808

ESP6500AA AF: 0.116 AC: 511

ESP6500EA AF: 0.439 AC: 3774

ExAC AF: 0.466 AC: 56584

Asia WGS AF: 0.535 AC: 1861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.019	T;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.012
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.50	T;T;T
MetaRNN	Benign	0.0000056	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.86	L;.;.
PhyloP100		5.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.094
Sift	Benign	0.64	T;T;T
Sift4G	Benign	0.41	T;T;T
Polyphen		0.011	B;.;.
Vest4		0.061
MPC		0.45
ClinPred		0.035	T
GERP RS		4.5
Varity_R		0.13
gMVP		0.42
Mutation Taster		=84/16	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: rs2290532; hg19: chr3-31789582; COSMIC: COSV67339761;