rs9635963

Variant names:

• chr18-24169651-G-A
• rs9635963
• NM_080597.4:c.2418+676C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080597.4(OSBPL1A):​c.2418+676C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,082 control chromosomes in the GnomAD database, including 31,002 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (31002 hom., cov: 32)
• Consequence: OSBPL1A NM_080597.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 18 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

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.2418+676C>T		intron	N/A	NP_542164.2
	OSBPL1A	NM_001242508.1		c.1272+676C>T		intron	N/A	NP_001229437.1	Q9BXW6-4
	OSBPL1A	NM_018030.4		c.879+676C>T		intron	N/A	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.2418+676C>T		intron	N/A	ENSP00000320291.3	Q9BXW6-1
	OSBPL1A	ENST00000399443.7	TSL:1	c.879+676C>T		intron	N/A	ENSP00000382372.3	Q9BXW6-2
	OSBPL1A	ENST00000880335.1		c.2418+676C>T		intron	N/A	ENSP00000550394.1

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91851 AN: 151966 Hom.: 30997 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.665

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.604 AC: 91874 AN: 152082 Hom.: 31002 Cov.: 32 AF XY: 0.602 AC XY: 44770 AN XY: 74342

African (AFR) AF: 0.299 AC: 12403 AN: 41482

American (AMR) AF: 0.656 AC: 10028 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2869 AN: 3472

East Asian (EAS) AF: 0.393 AC: 2031 AN: 5164

South Asian (SAS) AF: 0.681 AC: 3287 AN: 4826

European-Finnish (FIN) AF: 0.645 AC: 6808 AN: 10562

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52077 AN: 67988

Other (OTH) AF: 0.665 AC: 1401 AN: 2106

Alfa AF: 0.713 Hom.: 144869

Bravo AF: 0.585

Asia WGS AF: 0.535 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.73
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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: rs9635963; hg19: chr18-21749615;