rs924149914

Variant names:

• chr18-24178102-G-C
• rs924149914
• NM_080597.4:c.2004C>G

Your query was ambiguous. Multiple possible variants found:

• chr18-24178102-G-C
• chr18-24178102-G-A
• chr18-24178102-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_080597.4(OSBPL1A):​c.2004C>G​(p.Ile668Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,609,014 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 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000018 (0 hom.)
• Consequence: OSBPL1A NM_080597.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.56
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24318129).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL1A	NM_080597.4	MANE Select	c.2004C>G	p.Ile668Met	missense	Exon 21 of 28	NP_542164.2
	OSBPL1A	NM_001242508.1		c.858C>G	p.Ile286Met	missense	Exon 9 of 16	NP_001229437.1	Q9BXW6-4
	OSBPL1A	NM_018030.4		c.465C>G	p.Ile155Met	missense	Exon 7 of 14	NP_060500.3	Q9BXW6-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL1A	ENST00000319481.8	TSL:1 MANE Select	c.2004C>G	p.Ile668Met	missense	Exon 21 of 28	ENSP00000320291.3	Q9BXW6-1
	OSBPL1A	ENST00000399443.7	TSL:1	c.465C>G	p.Ile155Met	missense	Exon 7 of 14	ENSP00000382372.3	Q9BXW6-2
	OSBPL1A	ENST00000880335.1		c.2004C>G	p.Ile668Met	missense	Exon 21 of 28	ENSP00000550394.1

Frequencies

GnomAD3 genomes AF: 0.0000398 AC: 6 AN: 150856 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000663

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: 0.0000589

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251470 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000178 AC: 26 AN: 1458158 Hom.: 0 Cov.: 32 AF XY: 0.0000165 AC XY: 12 AN XY: 725370

African (AFR) AF: 0.00 AC: 0 AN: 33350

American (AMR) AF: 0.0000897 AC: 4 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26010

East Asian (EAS) AF: 0.00 AC: 0 AN: 39528

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52920

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1109622

Other (OTH) AF: 0.0000166 AC: 1 AN: 60170

GnomAD4 genome AF: 0.0000398 AC: 6 AN: 150856 Hom.: 0 Cov.: 32 AF XY: 0.0000408 AC XY: 3 AN XY: 73610

African (AFR) AF: 0.0000244 AC: 1 AN: 40978

American (AMR) AF: 0.0000663 AC: 1 AN: 15094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.00 AC: 0 AN: 4726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10324

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

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67872

Other (OTH) AF: 0.00 AC: 0 AN: 2076

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000416

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	0.086
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.46
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.6
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.10
Sift	Benign	0.071	T
Sift4G	Benign	0.10	T
Polyphen		0.81	P
Vest4		0.26
MutPred		0.42		Loss of catalytic residue at I668 (P = 0.0173)
MVP		0.40
MPC		0.70
ClinPred		0.25	T
GERP RS		5.1
Varity_R		0.72
gMVP		0.50
Mutation Taster		=56/44	polymorphism

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: rs924149914; hg19: chr18-21758066;