Variant 17-47814551-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145798.3(OSBPL7):c.1321G>T(p.Asp441Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,436,682 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 1 hom. )

Consequence

OSBPL7
NM_145798.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Variant links:

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]

OSBPL7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OSBPL7	NM_145798.3 link	c.1321G>T	p.Asp441Tyr	missense_variant	14/23	ENST00000007414.8	NP_665741.1	Q9BZF2-1Q8WXP9
OSBPL7	XM_047435292.1 link	c.1321G>T	p.Asp441Tyr	missense_variant	14/23		XP_047291248.1
OSBPL7	XM_047435293.1 link	c.1267G>T	p.Asp423Tyr	missense_variant	13/22		XP_047291249.1
OSBPL7	XR_934362.2 link	n.1537G>T		non_coding_transcript_exon_variant	14/22

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OSBPL7	ENST00000007414.8 link	c.1321G>T	p.Asp441Tyr	missense_variant	14/23	1	NM_145798.3	ENSP00000007414.3		Q9BZF2-1
OSBPL7	ENST00000613735.4 link	n.*245+787G>T		intron_variant		1		ENSP00000479827.1		Q9BZF2-2

Frequencies

GnomAD3 genomes

AF:

0.000117

AC:

AN:

145132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000399

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000686

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251050

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135744

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1291550

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

641134

show subpopulations

Gnomad4 AFR exome

AF:

0.000492

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000409

GnomAD4 genome

AF:

0.000117

AC:

AN:

145132

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

70536

show subpopulations

Gnomad4 AFR

AF:

0.000399

Gnomad4 AMR

AF:

0.0000686

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 30, 2023

The c.1321G>T (p.D441Y) alteration is located in exon 14 (coding exon 13) of the OSBPL7 gene. This alteration results from a G to T substitution at nucleotide position 1321, causing the aspartic acid (D) at amino acid position 441 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-0.00027

Eigen_PC

Benign

0.073

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.82

.;T

M_CAP

Benign

0.0090

MetaRNN

Uncertain

0.45

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

0.38

B;B

Vest4

0.59

MVP

0.56

MPC

0.90

ClinPred

0.47

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over