2-178324247-C-T

Variant names:

• chr2-178324247-C-T
• rs34874235
• NM_032523.4:c.173C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032523.4(OSBPL6):​c.173C>T​(p.Pro58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,573,804 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P58Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0023 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0037 (64 hom.)
• Consequence: OSBPL6 NM_032523.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038986504).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00234 (356/152320) while in subpopulation SAS AF = 0.0247 (119/4822). AF 95% confidence interval is 0.0211. There are 3 homozygotes in GnomAd4. There are 188 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 gene

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.173C>T	p.Pro58Leu	missense	Exon 4 of 25	NP_115912.1	Q9BZF3-1
	OSBPL6	NM_001201480.2		c.173C>T	p.Pro58Leu	missense	Exon 4 of 26	NP_001188409.1	Q9BZF3-5
	OSBPL6	NM_145739.3		c.110C>T	p.Pro37Leu	missense	Exon 2 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.173C>T	p.Pro58Leu	missense	Exon 4 of 25	ENSP00000190611.4	Q9BZF3-1
	OSBPL6	ENST00000392505.6	TSL:1	c.173C>T	p.Pro58Leu	missense	Exon 4 of 26	ENSP00000376293.2	Q9BZF3-5
	OSBPL6	ENST00000409631.5	TSL:1	c.173C>T	p.Pro58Leu	missense	Exon 3 of 23	ENSP00000386885.1	Q9BZF3-2

Frequencies

GnomAD3 genomes AF: 0.00233 AC: 355 AN: 152202 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0242

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00270

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00464 AC: 983 AN: 211822 AF XY: 0.00585

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.00100

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000180

Gnomad FIN exome AF: 0.0000519

Gnomad NFE exome AF: 0.00297

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00368 AC: 5231 AN: 1421484 Hom.: 64 Cov.: 30 AF XY: 0.00431 AC XY: 3033 AN XY: 703284

African (AFR) AF: 0.000485 AC: 16 AN: 32974

American (AMR) AF: 0.00118 AC: 50 AN: 42548

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 3 AN: 25282

East Asian (EAS) AF: 0.0000773 AC: 3 AN: 38814

South Asian (SAS) AF: 0.0243 AC: 1979 AN: 81284

European-Finnish (FIN) AF: 0.0000587 AC: 3 AN: 51122

Middle Eastern (MID) AF: 0.00968 AC: 55 AN: 5680

European-Non Finnish (NFE) AF: 0.00268 AC: 2907 AN: 1085298

Other (OTH) AF: 0.00368 AC: 215 AN: 58482

GnomAD4 genome AF: 0.00234 AC: 356 AN: 152320 Hom.: 3 Cov.: 33 AF XY: 0.00252 AC XY: 188 AN XY: 74476

African (AFR) AF: 0.000553 AC: 23 AN: 41562

American (AMR) AF: 0.00124 AC: 19 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4822

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00270 AC: 184 AN: 68024

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.00263 Hom.: 0

Bravo AF: 0.00179

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00279 AC: 24

ExAC AF: 0.00461 AC: 551

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.094
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.96	D
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.5
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.025
Sift	Uncertain	0.022	D
Sift4G	Benign	0.18	T
Polyphen		0.065	B
Vest4		0.30
MVP		0.068
MPC		0.34
ClinPred		0.0077	T
GERP RS		5.0
Varity_R		0.071
gMVP		0.27
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.010		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: rs34874235; hg19: chr2-179188974;