chr22-36253528-G-A

Position:

• chr22-36253528-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003661.4(APOL1):​c.-20+309G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,196 control chromosomes in the GnomAD database, including 2,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2038 hom., cov: 32)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.409

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 22-36253528-G-A is Benign according to our data. Variant chr22-36253528-G-A is described in ClinVar as [Benign]. Clinvar id is 1277110.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL1	NM_003661.4	c.-20+309G>A		intron_variant		ENST00000397278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL1	ENST00000397278.8	c.-20+309G>A		intron_variant		1	NM_003661.4	A2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23964 AN: 152078 Hom.: 2034 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.0437

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.158 AC: 23976 AN: 152196 Hom.: 2038 Cov.: 32 AF XY: 0.158 AC XY: 11742 AN XY: 74402

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0438

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.185

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.142

Alfa AF: 0.177 Hom.: 4104

Bravo AF: 0.149

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.45

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: rs9610467; hg19: chr22-36649574;