22-36254094-A-G

Variant names:

• chr22-36254094-A-G
• rs117463237
• NM_003661.4:c.-19-843A>G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003661.4(APOL1):​c.-19-843A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,389,302 control chromosomes in the GnomAD database, including 69 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0082 (8 hom., cov: 32)
  • Exomes 𝑓: 0.0087 (61 hom.)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0790

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 22-36254094-A-G is Benign according to our data. Variant chr22-36254094-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316242.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4	c.-19-843A>G		intron_variant	Intron 1 of 5	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8	c.-19-843A>G		intron_variant	Intron 1 of 5	1	NM_003661.4	ENSP00000380448.4

Frequencies

GnomAD3 genomes AF: 0.00824 AC: 1254 AN: 152126 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00291

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.00908

GnomAD4 exome AF: 0.00870 AC: 10760 AN: 1237058 Hom.: 61 AF XY: 0.00868 AC XY: 5411 AN XY: 623404

Gnomad4 AFR exome AF: 0.00170

Gnomad4 AMR exome AF: 0.00956

Gnomad4 ASJ exome AF: 0.0222

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00314

Gnomad4 FIN exome AF: 0.0127

Gnomad4 NFE exome AF: 0.00910

Gnomad4 OTH exome AF: 0.00959

GnomAD4 genome AF: 0.00824 AC: 1254 AN: 152244 Hom.: 8 Cov.: 32 AF XY: 0.00857 AC XY: 638 AN XY: 74448

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.0182

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00865 Hom.: 1

Bravo AF: 0.00760

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 20, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.52

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: rs117463237; hg19: chr22-36650140;