NM_145798.3:c.1406C>T

Variant names:

• chr17-47813780-G-A
• rs759528896
• NM_145798.3:c.1406C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_145798.3(OSBPL7):​c.1406C>T​(p.Ala469Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000304 in 1,612,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000026 (0 hom.)
• Consequence: OSBPL7 NM_145798.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.60
• Publications: 1 publications found

Genes affected

OSBPL7 (HGNC:16387): (oxysterol binding protein like 7) 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. Two transcript variants encoding the same isoform have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22911984).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145798.3. 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
	OSBPL7	NM_145798.3	MANE Select	c.1406C>T	p.Ala469Val	missense	Exon 15 of 23	NP_665741.1	Q9BZF2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL7	ENST00000007414.8	TSL:1 MANE Select	c.1406C>T	p.Ala469Val	missense	Exon 15 of 23	ENSP00000007414.3	Q9BZF2-1
	OSBPL7	ENST00000613735.4	TSL:1	n.*245+1558C>T		intron	N/A	ENSP00000479827.1	Q9BZF2-2
	OSBPL7	ENST00000915866.1		c.1406C>T	p.Ala469Val	missense	Exon 15 of 23	ENSP00000585925.1

Frequencies

GnomAD3 genomes AF: 0.0000723 AC: 11 AN: 152168 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000321 AC: 8 AN: 248950 AF XY: 0.0000444

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000164

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000260 AC: 38 AN: 1460618 Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 13 AN XY: 726672

African (AFR) AF: 0.000239 AC: 8 AN: 33474

American (AMR) AF: 0.0000447 AC: 2 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.0000191 AC: 1 AN: 52398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111872

Other (OTH) AF: 0.0000166 AC: 1 AN: 60374

GnomAD4 genome AF: 0.0000723 AC: 11 AN: 152168 Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5 AN XY: 74338

African (AFR) AF: 0.000241 AC: 10 AN: 41422

American (AMR) AF: 0.00 AC: 0 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.0000642

ExAC AF: 0.0000495 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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	0.14
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.56
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.19
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.6
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.10
Sift	Benign	0.066	T
Sift4G	Benign	0.16	T
Polyphen		0.43	B
Vest4		0.50
MutPred		0.59		Gain of catalytic residue at A469 (P = 0.0541)
MVP		0.46
MPC		0.88
ClinPred		0.16	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs759528896; hg19: chr17-45891146; COSMIC: COSV50113774; COSMIC: COSV50113774;