22-36254766-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003661.4(APOL1):c.-19-171G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00862 in 723,788 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0063 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0092 (40 hom.)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.73

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=-0.92).
• BP6: Variant 22-36254766-G-T is Benign according to our data. Variant chr22-36254766-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1706719.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00634 (964/152160) while in subpopulation SAS AF= 0.0189 (91/4818). AF 95% confidence interval is 0.0158. There are 9 homozygotes in gnomad4. There are 475 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL1	NM_003661.4	c.-19-171G>T		intron_variant		ENST00000397278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL1	ENST00000397278.8	c.-19-171G>T		intron_variant		1	NM_003661.4	A2

Frequencies

GnomAD3 genomes AF: 0.00635 AC: 966 AN: 152042 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.00775

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00888

Gnomad OTH AF: 0.00527

GnomAD4 exome AF: 0.00923 AC: 5276 AN: 571628 Hom.: 40 AF XY: 0.00985 AC XY: 2941 AN XY: 298644

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00387

Gnomad4 ASJ exome AF: 0.00703

Gnomad4 EAS exome AF: 0.0000411

Gnomad4 SAS exome AF: 0.0195

Gnomad4 FIN exome AF: 0.00859

Gnomad4 NFE exome AF: 0.00928

Gnomad4 OTH exome AF: 0.00755

GnomAD4 genome AF: 0.00634 AC: 964 AN: 152160 Hom.: 9 Cov.: 32 AF XY: 0.00639 AC XY: 475 AN XY: 74376

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.00589

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.00775

Gnomad4 NFE AF: 0.00887

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.00889 Hom.: 2

Bravo AF: 0.00546

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.085
Dann	Benign	0.60

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: rs192737055; hg19: chr22-36650812;