rs136148

Variant names:

• chr22-36256885-C-T
• rs136148
• NM_003661.4:c.45-198C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003661.4(APOL1):​c.45-198C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 152,080 control chromosomes in the GnomAD database, including 41,917 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (41917 hom., cov: 32)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.22
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 22-36256885-C-T is Benign according to our data. Variant chr22-36256885-C-T is described in ClinVar as Benign. ClinVar VariationId is 1264808.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4	c.45-198C>T		intron_variant	Intron 2 of 5	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8	c.45-198C>T		intron_variant	Intron 2 of 5	1	NM_003661.4	ENSP00000380448.4

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112107 AN: 151962 Hom.: 41879 Cov.: 32

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.694

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

GnomAD4 genome AF: 0.738 AC: 112205 AN: 152080 Hom.: 41917 Cov.: 32 AF XY: 0.741 AC XY: 55102 AN XY: 74342

African (AFR) AF: 0.839 AC: 34801 AN: 41474

American (AMR) AF: 0.764 AC: 11678 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 2236 AN: 3470

East Asian (EAS) AF: 0.799 AC: 4140 AN: 5184

South Asian (SAS) AF: 0.777 AC: 3749 AN: 4828

European-Finnish (FIN) AF: 0.695 AC: 7350 AN: 10576

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.678 AC: 46091 AN: 67940

Other (OTH) AF: 0.695 AC: 1468 AN: 2112

Alfa AF: 0.697 Hom.: 160593

Bravo AF: 0.745

Asia WGS AF: 0.788 AC: 2739 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: 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	-0.91
CADD	Benign	0.070
DANN	Benign	0.39
PhyloP100		-1.2
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: rs136148; hg19: chr22-36652931; COSMIC: COSV59868232;