NM_003661.4:c.187+692T>A

Variant names:

• chr22-36258099-T-A
• rs136150
• NM_003661.4:c.187+692T>A

Variant summary

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

The NM_003661.4(APOL1):​c.187+692T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 152,072 control chromosomes in the GnomAD database, including 52,103 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 0.83 (52103 hom., cov: 32)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.88 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4	c.187+692T>A		intron_variant	Intron 4 of 5	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8	c.187+692T>A		intron_variant	Intron 4 of 5	1	NM_003661.4	ENSP00000380448.4

Frequencies

GnomAD3 genomes AF: 0.826 AC: 125500 AN: 151954 Hom.: 52058 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.857

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.826 AC: 125603 AN: 152072 Hom.: 52103 Cov.: 32 AF XY: 0.829 AC XY: 61632 AN XY: 74356

African (AFR) AF: 0.888 AC: 36839 AN: 41506

American (AMR) AF: 0.858 AC: 13111 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2718 AN: 3462

East Asian (EAS) AF: 0.842 AC: 4347 AN: 5164

South Asian (SAS) AF: 0.830 AC: 3997 AN: 4818

European-Finnish (FIN) AF: 0.812 AC: 8617 AN: 10606

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.786 AC: 53405 AN: 67912

Other (OTH) AF: 0.810 AC: 1713 AN: 2116

Alfa AF: 0.807 Hom.: 5799

Bravo AF: 0.833

Asia WGS AF: 0.837 AC: 2912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.5
DANN	Benign	0.39
PhyloP100		-0.027
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: rs136150; hg19: chr22-36654145; COSMIC: COSV59868258; COSMIC: COSV59868258;