rs7284919

Variant names:

• chr22-36256118-T-C
• rs7284919
• NM_003661.4:c.45-965T>C

Variant summary

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

The ENST00000397278.8(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 ENST00000397278.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 5 publications found

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]

APOL1 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 4, susceptibility to

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397278.8. 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
	APOL1	NM_003661.4	MANE Select	c.45-965T>C		intron	N/A	NP_003652.2
	APOL1	NM_145343.3		c.93-965T>C		intron	N/A	NP_663318.1
	APOL1	NM_001136540.2		c.45-965T>C		intron	N/A	NP_001130012.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL1	ENST00000397278.8	TSL:1 MANE Select	c.45-965T>C		intron	N/A	ENSP00000380448.4
	APOL1	ENST00000319136.8	TSL:1	c.93-965T>C		intron	N/A	ENSP00000317674.4
	APOL1	ENST00000438034.6	TSL:4	c.132-965T>C		intron	N/A	ENSP00000404525.2

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

African (AFR) AF: 0.109 AC: 4513 AN: 41554

American (AMR) AF: 0.115 AC: 1755 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 359 AN: 3468

East Asian (EAS) AF: 0.0464 AC: 241 AN: 5192

South Asian (SAS) AF: 0.150 AC: 724 AN: 4830

European-Finnish (FIN) AF: 0.122 AC: 1296 AN: 10612

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10570 AN: 68010

Other (OTH) AF: 0.121 AC: 255 AN: 2108

Alfa AF: 0.143 Hom.: 2942

Bravo AF: 0.125

Asia WGS AF: 0.0800 AC: 278 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.34
PhyloP100		-0.012
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: rs7284919; hg19: chr22-36652164;