chr7-24800272-C-T

Variant names:

• chr7-24800272-C-T
• rs139154799
• NM_015550.4:c.2575G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_015550.4(OSBPL3):​c.2575G>A​(p.Asp859Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00247 in 1,604,726 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (16 hom.)
• Consequence: OSBPL3 NM_015550.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.269
• Publications: 8 publications found

Genes affected

OSBPL3 (HGNC:16370): (oxysterol binding protein like 3) This gene encodes a member of the oxysterol-binding protein (OSBP) family, a group of intracellular lipid receptors. Most members contain an N-terminal pleckstrin homology domain and a highly conserved C-terminal OSBP-like sterol-binding domain. The encoded protein is involved in the regulation of cell adhesion and organization of the actin cytoskeleton. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004227251).
• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015550.4. 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
	OSBPL3	NM_015550.4	MANE Select	c.2575G>A	p.Asp859Asn	missense	Exon 23 of 23	NP_056365.1	Q9H4L5-1
	OSBPL3	NM_145320.2		c.2482G>A	p.Asp828Asn	missense	Exon 21 of 21	NP_663160.1	Q9H4L5-2
	OSBPL3	NM_145321.2		c.2467G>A	p.Asp823Asn	missense	Exon 21 of 21	NP_663161.1	Q9H4L5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL3	ENST00000313367.7	TSL:1 MANE Select	c.2575G>A	p.Asp859Asn	missense	Exon 23 of 23	ENSP00000315410.2	Q9H4L5-1
	OSBPL3	ENST00000396431.5	TSL:1	c.2482G>A	p.Asp828Asn	missense	Exon 21 of 21	ENSP00000379708.1	Q9H4L5-2
	OSBPL3	ENST00000396429.5	TSL:1	c.2467G>A	p.Asp823Asn	missense	Exon 21 of 21	ENSP00000379706.1	Q9H4L5-3

Frequencies

GnomAD3 genomes AF: 0.00158 AC: 241 AN: 152090 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000628

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00290

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00124 AC: 311 AN: 250694 AF XY: 0.00140

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.000783

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00226

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00256 AC: 3723 AN: 1452518 Hom.: 16 Cov.: 27 AF XY: 0.00251 AC XY: 1818 AN XY: 723180

African (AFR) AF: 0.000541 AC: 18 AN: 33244

American (AMR) AF: 0.000761 AC: 34 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26044

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39614

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86028

European-Finnish (FIN) AF: 0.000281 AC: 15 AN: 53308

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5760

European-Non Finnish (NFE) AF: 0.00315 AC: 3477 AN: 1103806

Other (OTH) AF: 0.00266 AC: 160 AN: 60046

GnomAD4 genome AF: 0.00158 AC: 241 AN: 152208 Hom.: 0 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74406

African (AFR) AF: 0.000626 AC: 26 AN: 41536

American (AMR) AF: 0.000785 AC: 12 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00290 AC: 197 AN: 67994

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00236 Hom.: 1

Bravo AF: 0.00158

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00233 AC: 20

ExAC AF: 0.00138 AC: 168

EpiCase AF: 0.00289

EpiControl AF: 0.00219

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.13
DANN	Benign	0.69
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.27
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.34	N
REVEL	Benign	0.089
Sift	Benign	0.51	T
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.12
MVP		0.15
MPC		0.21
ClinPred		0.0025	T
GERP RS		-11
Varity_R		0.035
gMVP		0.21
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs139154799; hg19: chr7-24839891; COSMIC: COSV99046333;