chr22-36262488-C-T

Variant names:

• chr22-36262488-C-T
• rs713753
• NM_003661.4:c.314+766C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003661.4. 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.314+766C>T		intron	N/A	NP_003652.2
	APOL1	NM_145343.3		c.362+766C>T		intron	N/A	NP_663318.1
	APOL1	NM_001136540.2		c.314+766C>T		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.314+766C>T		intron	N/A	ENSP00000380448.4
	APOL1	ENST00000319136.8	TSL:1	c.362+766C>T		intron	N/A	ENSP00000317674.4
	APOL1	ENST00000438034.6	TSL:4	c.401+766C>T		intron	N/A	ENSP00000404525.2

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

African (AFR) AF: 0.222 AC: 9223 AN: 41466

American (AMR) AF: 0.669 AC: 10224 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2293 AN: 3468

East Asian (EAS) AF: 0.755 AC: 3900 AN: 5164

South Asian (SAS) AF: 0.672 AC: 3233 AN: 4810

European-Finnish (FIN) AF: 0.654 AC: 6909 AN: 10570

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40093 AN: 67968

Other (OTH) AF: 0.557 AC: 1174 AN: 2108

Alfa AF: 0.570 Hom.: 106626

Bravo AF: 0.501

Asia WGS AF: 0.718 AC: 2495 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.091
DANN	Benign	0.43
PhyloP100		-0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.96
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: rs713753; hg19: chr22-36658534; COSMIC: COSV59868355; COSMIC: COSV59868355;