rs7284919

chr22-36256118-T-C

Variant summary

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

The NM_003661.4(APOL1):c.45-965T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,284 control chromosomes in the GnomAD database, including 1,361 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 0.13 (1361 hom., cov: 31)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL1	NM_003661.4	c.45-965T>C		intron_variant		ENST00000397278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL1	ENST00000397278.8	c.45-965T>C		intron_variant		1	NM_003661.4	A2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19794 AN: 152166 Hom.: 1360 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0463

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.130 AC: 19798 AN: 152284 Hom.: 1361 Cov.: 31 AF XY: 0.129 AC XY: 9636 AN XY: 74460

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0464

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.121

Alfa AF: 0.146 Hom.: 2167

Bravo AF: 0.125

Asia WGS AF: 0.0800 AC: 278 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	1.5
Dann	Benign	0.34

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: rs7284919; hg19: chr22-36652164;