chr7-24974363-A-G

Variant names:

• chr7-24974363-A-G
• rs10486445
• NM_015550.4:c.-150+5523T>C

Variant summary

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

The NM_015550.4(OSBPL3):​c.-150+5523T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,178 control chromosomes in the GnomAD database, including 7,320 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 0.29 (7320 hom., cov: 33)
• Consequence: OSBPL3 NM_015550.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 6 publications found

Genes affected

OSBPL3 (HGNC:16370): (oxysterol binding protein like 3) 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. The encoded protein is involved in the regulation of cell adhesion and organization of the actin cytoskeleton. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OSBPL3	NM_015550.4	c.-150+5523T>C		intron_variant	Intron 1 of 22	ENST00000313367.7	NP_056365.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OSBPL3	ENST00000313367.7	c.-150+5523T>C		intron_variant	Intron 1 of 22	1	NM_015550.4	ENSP00000315410.2
OSBPL3	ENST00000415952.1	c.-150+7036T>C		intron_variant	Intron 1 of 2	4		ENSP00000411249.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44586 AN: 152060 Hom.: 7323 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.321

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

GnomAD4 genome AF: 0.293 AC: 44589 AN: 152178 Hom.: 7320 Cov.: 33 AF XY: 0.284 AC XY: 21159 AN XY: 74394

African (AFR) AF: 0.184 AC: 7661 AN: 41530

American (AMR) AF: 0.271 AC: 4145 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1016 AN: 3472

East Asian (EAS) AF: 0.0127 AC: 66 AN: 5190

South Asian (SAS) AF: 0.166 AC: 802 AN: 4828

European-Finnish (FIN) AF: 0.323 AC: 3412 AN: 10574

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26488 AN: 67970

Other (OTH) AF: 0.317 AC: 671 AN: 2114

Alfa AF: 0.352 Hom.: 30714

Bravo AF: 0.282

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.48
PhyloP100		0.34
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: rs10486445; hg19: chr7-25013982;