rs10521916

Positions:

• chrX-23877337-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024122.5(APOO):​c.237+1578C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0332 in 112,184 control chromosomes in the GnomAD database, including 63 homozygotes. There are 1,075 hemizygotes in GnomAD. 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 0.033 (63 hom., 1075 hem., cov: 23)
• Consequence: APOO NM_024122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.832

Genes affected

APOO (HGNC:28727): (apolipoprotein O) This gene is a member of the apolipoprotein family. Members of this protein family are involved in the transport and metabolism of lipids. The encoded protein associates with HDL, LDL and VLDL lipoproteins and is characterized by chondroitin-sulfate glycosylation. This protein may be involved in preventing lipid accumulation in the myocardium in obese and diabetic patients. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 4, 5, 12 and 16.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOO	NM_024122.5	c.237+1578C>T		intron_variant		ENST00000379226.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOO	ENST00000379226.9	c.237+1578C>T		intron_variant		1	NM_024122.5	P1

Frequencies

GnomAD3 genomes AF: 0.0332 AC: 3722 AN: 112131 Hom.: 63 Cov.: 23 AF XY: 0.0313 AC XY: 1074 AN XY: 34331

Gnomad AFR AF: 0.00718

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00831

Gnomad FIN AF: 0.0289

Gnomad MID AF: 0.0502

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0422

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

GnomAD4 genome AF: 0.0332 AC: 3722 AN: 112184 Hom.: 63 Cov.: 23 AF XY: 0.0313 AC XY: 1075 AN XY: 34394

Gnomad4 AFR AF: 0.00716

Gnomad4 AMR AF: 0.0353

Gnomad4 ASJ AF: 0.0328

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00870

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0417

Alfa AF: 0.0399 Hom.: 227

Bravo AF: 0.0322

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.2
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs10521916; hg19: chrX-23895454;