Genetic Variant NM_080597.4:c.1913A>G (chr18-24178193-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_080597.4(OSBPL1A):c.1913A>G(p.Asp638Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000261 in 1,477,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

OSBPL1A
NM_080597.4 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01

Publications

2 publications found

Variant links:

Genes affected

OSBPL1A (HGNC:16398): (oxysterol binding protein like 1A) 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, although some members contain only the sterol-binding domain. Transcript variants derived from alternative promoter usage and/or alternative splicing exist; they encode different isoforms. [provided by RefSeq, Jul 2008]

OSBPL1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.09290865).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080597.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSBPL1A	NM_080597.4	MANE Select	c.1913A>G	p.Asp638Gly	missense splice_region	Exon 21 of 28	NP_542164.2
OSBPL1A	NM_001242508.1		c.767A>G	p.Asp256Gly	missense splice_region	Exon 9 of 16	NP_001229437.1	Q9BXW6-4
OSBPL1A	NM_018030.4		c.374A>G	p.Asp125Gly	missense splice_region	Exon 7 of 14	NP_060500.3	Q9BXW6-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OSBPL1A	ENST00000319481.8	TSL:1 MANE Select	c.1913A>G	p.Asp638Gly	missense splice_region	Exon 21 of 28	ENSP00000320291.3	Q9BXW6-1
OSBPL1A	ENST00000399443.7	TSL:1	c.374A>G	p.Asp125Gly	missense splice_region	Exon 7 of 14	ENSP00000382372.3	Q9BXW6-2
OSBPL1A	ENST00000880335.1		c.1913A>G	p.Asp638Gly	missense splice_region	Exon 21 of 28	ENSP00000550394.1

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

145914

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000686

Gnomad ASJ

AF:

0.00116

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000313

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000181

AC:

AN:

204914

AF XY:

0.000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00227

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000171

Gnomad OTH exome

AF:

0.000868

GnomAD4 exome

AF:

0.000270

AC:

359

AN:

1331226

Hom.:

Cov.:

AF XY:

0.000263

AC XY:

173

AN XY:

656862

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29150

American (AMR)

AF:

0.00

AC:

AN:

30854

Ashkenazi Jewish (ASJ)

AF:

0.00272

AC:

AN:

21704

East Asian (EAS)

AF:

0.00

AC:

AN:

38242

South Asian (SAS)

AF:

0.00

AC:

AN:

66246

European-Finnish (FIN)

AF:

0.0000208

AC:

AN:

48152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5110

European-Non Finnish (NFE)

AF:

0.000285

AC:

296

AN:

1038050

Other (OTH)

AF:

0.0000558

AC:

AN:

53718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000178

AC:

AN:

145914

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

70712

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

38820

American (AMR)

AF:

0.0000686

AC:

AN:

14584

Ashkenazi Jewish (ASJ)

AF:

0.00116

AC:

AN:

3446

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00

AC:

AN:

4626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8992

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.000313

AC:

AN:

67146

Other (OTH)

AF:

0.00

AC:

AN:

2000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000366

Hom.:

Bravo

AF:

0.000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000107

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.021

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

8.0

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.21

Sift

Benign

0.043

Sift4G

Uncertain

0.042

Polyphen

0.65

Vest4

0.36

MVP

0.44

MPC

1.4

ClinPred

0.19

GERP RS

5.7

Varity_R

0.55

gMVP

0.66

Mutation Taster

=27/73

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over