12-12726636-T-C

Variant names:

• chr12-12726636-T-C
• rs34322
• ENST00000326765.10:c.96+540T>C

Variant summary

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

The ENST00000326765.10(APOLD1):​c.96+540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,930 control chromosomes in the GnomAD database, including 19,457 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 0.50 (19457 hom., cov: 32)
• Consequence: APOLD1 ENST00000326765.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.596
• Publications: 23 publications found

Genes affected

APOLD1 (HGNC:25268): (apolipoprotein L domain containing 1) APOLD1 is an endothelial cell early response protein that may play a role in regulation of endothelial cell signaling and vascular function (Regard et al., 2004 [PubMed 15102925]).[supplied by OMIM, Dec 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000326765.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOLD1	NM_001130415.2		c.96+540T>C		intron	N/A	NP_001123887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOLD1	ENST00000326765.10	TSL:1	c.96+540T>C		intron	N/A	ENSP00000324277.6
	APOLD1	ENST00000534843.1	TSL:2	n.*50+263T>C		intron	N/A	ENSP00000456719.1
	APOLD1	ENST00000540583.5	TSL:4	n.*50+263T>C		intron	N/A	ENSP00000454511.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76222 AN: 151812 Hom.: 19444 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.538

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.502 AC: 76268 AN: 151930 Hom.: 19457 Cov.: 32 AF XY: 0.503 AC XY: 37351 AN XY: 74236

African (AFR) AF: 0.430 AC: 17817 AN: 41390

American (AMR) AF: 0.468 AC: 7143 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1747 AN: 3466

East Asian (EAS) AF: 0.488 AC: 2524 AN: 5172

South Asian (SAS) AF: 0.531 AC: 2557 AN: 4818

European-Finnish (FIN) AF: 0.593 AC: 6261 AN: 10554

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.538 AC: 36541 AN: 67950

Other (OTH) AF: 0.486 AC: 1025 AN: 2110

Alfa AF: 0.522 Hom.: 59167

Bravo AF: 0.490

Asia WGS AF: 0.483 AC: 1682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34322; hg19: chr12-12879570;