NM_003661.4:c.-19-27G>A

Variant names:

• chr22-36254910-G-A
• rs9610468
• NM_003661.4:c.-19-27G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003661.4(APOL1):​c.-19-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,612,258 control chromosomes in the GnomAD database, including 25,788 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1809 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23979 hom.)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.312
• Publications: 8 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 22-36254910-G-A is Benign according to our data. Variant chr22-36254910-G-A is described in ClinVar as Benign. ClinVar VariationId is 1290711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL1	NM_003661.4	MANE Select	c.-19-27G>A		intron	N/A	NP_003652.2
	APOL1	NM_001136540.2		c.-46G>A		5_prime_UTR	Exon 2 of 6	NP_001130012.1	O14791-1
	APOL1	NM_001362927.2		c.-46G>A		5_prime_UTR	Exon 2 of 5	NP_001349856.1	O14791-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL1	ENST00000397278.8	TSL:1 MANE Select	c.-19-27G>A		intron	N/A	ENSP00000380448.4	O14791-1
	APOL1	ENST00000319136.8	TSL:1	c.30-27G>A		intron	N/A	ENSP00000317674.4	O14791-2
	APOL1	ENST00000438034.6	TSL:4	c.42G>A	p.Leu14Leu	synonymous	Exon 3 of 7	ENSP00000404525.2	B1AH94

Frequencies

GnomAD3 genomes AF: 0.141 AC: 21399 AN: 152076 Hom.: 1808 Cov.: 32

Gnomad AFR AF: 0.0649

Gnomad AMI AF: 0.0485

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.136

GnomAD2 exomes AF: 0.150 AC: 37692 AN: 251352 AF XY: 0.155

Gnomad AFR exome AF: 0.0653

Gnomad AMR exome AF: 0.0942

Gnomad ASJ exome AF: 0.166

Gnomad EAS exome AF: 0.0378

Gnomad FIN exome AF: 0.177

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.176 AC: 257191 AN: 1460064 Hom.: 23979 Cov.: 33 AF XY: 0.177 AC XY: 128303 AN XY: 726434

African (AFR) AF: 0.0635 AC: 2125 AN: 33462

American (AMR) AF: 0.0994 AC: 4443 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 4375 AN: 26098

East Asian (EAS) AF: 0.0530 AC: 2104 AN: 39682

South Asian (SAS) AF: 0.159 AC: 13680 AN: 86230

European-Finnish (FIN) AF: 0.182 AC: 9736 AN: 53370

Middle Eastern (MID) AF: 0.158 AC: 907 AN: 5744

European-Non Finnish (NFE) AF: 0.189 AC: 210287 AN: 1110468

Other (OTH) AF: 0.158 AC: 9534 AN: 60312

GnomAD4 genome AF: 0.141 AC: 21405 AN: 152194 Hom.: 1809 Cov.: 32 AF XY: 0.142 AC XY: 10532 AN XY: 74408

African (AFR) AF: 0.0651 AC: 2705 AN: 41558

American (AMR) AF: 0.124 AC: 1892 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.0472 AC: 244 AN: 5174

South Asian (SAS) AF: 0.144 AC: 692 AN: 4818

European-Finnish (FIN) AF: 0.185 AC: 1958 AN: 10588

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12959 AN: 67992

Other (OTH) AF: 0.133 AC: 281 AN: 2110

Alfa AF: 0.154 Hom.: 1156

Bravo AF: 0.130

Asia WGS AF: 0.0790 AC: 275 AN: 3478

EpiCase AF: 0.185

EpiControl AF: 0.189

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.58
PhyloP100		-0.31
Mutation Taster		=300/0	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: rs9610468; hg19: chr22-36650956; COSMIC: COSV59869580;