chr2-178339070-G-A

Variant names:

• chr2-178339070-G-A
• rs1434087
• NM_032523.4:c.870G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_032523.4(OSBPL6):​c.870G>A​(p.Ser290Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,610,878 control chromosomes in the GnomAD database, including 677,525 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 0.91 (63527 hom., cov: 32)
  • Exomes 𝑓: 0.92 (613998 hom.)
• Consequence: OSBPL6 NM_032523.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 21 publications found

Genes affected

OSBPL6 (HGNC:16388): (oxysterol binding protein like 6) 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. Transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=1.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032523.4. 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
	OSBPL6	NM_032523.4	MANE Select	c.870G>A	p.Ser290Ser	synonymous	Exon 10 of 25	NP_115912.1	Q9BZF3-1
	OSBPL6	NM_001201480.2		c.870G>A	p.Ser290Ser	synonymous	Exon 10 of 26	NP_001188409.1	Q9BZF3-5
	OSBPL6	NM_145739.3		c.807G>A	p.Ser269Ser	synonymous	Exon 8 of 24	NP_665682.1	Q9BZF3-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OSBPL6	ENST00000190611.9	TSL:1 MANE Select	c.870G>A	p.Ser290Ser	synonymous	Exon 10 of 25	ENSP00000190611.4	Q9BZF3-1
	OSBPL6	ENST00000392505.6	TSL:1	c.870G>A	p.Ser290Ser	synonymous	Exon 10 of 26	ENSP00000376293.2	Q9BZF3-5
	OSBPL6	ENST00000409631.5	TSL:1	c.870G>A	p.Ser290Ser	synonymous	Exon 9 of 23	ENSP00000386885.1	Q9BZF3-2

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138928 AN: 152166 Hom.: 63477 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.905

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.885

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.900

GnomAD2 exomes AF: 0.928 AC: 232437 AN: 250410 AF XY: 0.928

Gnomad AFR exome AF: 0.890

Gnomad AMR exome AF: 0.944

Gnomad ASJ exome AF: 0.907

Gnomad EAS exome AF: 0.967

Gnomad FIN exome AF: 0.946

Gnomad NFE exome AF: 0.915

Gnomad OTH exome AF: 0.922

GnomAD4 exome AF: 0.917 AC: 1338071 AN: 1458592 Hom.: 613998 Cov.: 37 AF XY: 0.918 AC XY: 666454 AN XY: 725754

African (AFR) AF: 0.891 AC: 29731 AN: 33380

American (AMR) AF: 0.941 AC: 41971 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.907 AC: 23690 AN: 26112

East Asian (EAS) AF: 0.973 AC: 38552 AN: 39618

South Asian (SAS) AF: 0.952 AC: 81964 AN: 86090

European-Finnish (FIN) AF: 0.943 AC: 50316 AN: 53330

Middle Eastern (MID) AF: 0.898 AC: 5157 AN: 5742

European-Non Finnish (NFE) AF: 0.912 AC: 1011622 AN: 1109430

Other (OTH) AF: 0.913 AC: 55068 AN: 60284

GnomAD4 genome AF: 0.913 AC: 139036 AN: 152286 Hom.: 63527 Cov.: 32 AF XY: 0.916 AC XY: 68169 AN XY: 74458

African (AFR) AF: 0.888 AC: 36894 AN: 41554

American (AMR) AF: 0.923 AC: 14118 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.905 AC: 3139 AN: 3468

East Asian (EAS) AF: 0.969 AC: 5025 AN: 5184

South Asian (SAS) AF: 0.951 AC: 4591 AN: 4828

European-Finnish (FIN) AF: 0.948 AC: 10060 AN: 10614

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62192 AN: 68028

Other (OTH) AF: 0.899 AC: 1901 AN: 2114

Alfa AF: 0.913 Hom.: 138548

Bravo AF: 0.910

Asia WGS AF: 0.954 AC: 3318 AN: 3478

EpiCase AF: 0.905

EpiControl AF: 0.904

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	9.8
DANN	Benign	0.62
PhyloP100		1.2
Mutation Taster		=84/16	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: rs1434087; hg19: chr2-179203797; COSMIC: COSV108010209;