22-36262488-C-T

Variant summary

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

The NM_003661.4(APOL1):c.314+766C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,046 control chromosomes in the GnomAD database, including 22,490 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 0.51 (22490 hom., cov: 32)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611

Genes affected

APOL1 (HGNC:618): (apolipoprotein L1) This gene encodes a secreted high density lipoprotein which binds to apolipoprotein A-I. Apolipoprotein A-I is a relatively abundant plasma protein and is the major apoprotein of HDL. It is involved in the formation of most cholesteryl esters in plasma and also promotes efflux of cholesterol from cells. This apolipoprotein L family member may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver. Several different transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL1	NM_003661.4	c.314+766C>T		intron_variant		ENST00000397278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL1	ENST00000397278.8	c.314+766C>T		intron_variant		1	NM_003661.4	A2

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77746 AN: 151928 Hom.: 22471 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.624

Gnomad AMR AF: 0.668

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.755

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.512 AC: 77788 AN: 152046 Hom.: 22490 Cov.: 32 AF XY: 0.523 AC XY: 38875 AN XY: 74354

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.557

Alfa AF: 0.584 Hom.: 52796

Bravo AF: 0.501

Asia WGS AF: 0.718 AC: 2495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.091
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.96

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: rs713753; hg19: chr22-36658534; COSMIC: COSV59868355; COSMIC: COSV59868355;