dbSNP rs199714563: APOL1:c.-19-66_-19-65delAA (chr22-36254862-CAA-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003661.4(APOL1):c.-19-66_-19-65delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000158 in 1,266,340 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

APOL1
NM_003661.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.189

Publications

0 publications found

Variant links:

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)

APOL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOL1	NM_003661.4	MANE Select	c.-19-66_-19-65delAA	intron	N/A	NP_003652.2
APOL1	NM_145343.3		c.30-66_30-65delAA	intron	N/A	NP_663318.1	O14791-2
APOL1	NM_001136540.2		c.-58-27_-58-26delAA	intron	N/A	NP_001130012.1	O14791-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
APOL1	ENST00000397278.8	TSL:1 MANE Select	c.-19-74_-19-73delAA	intron	N/A	ENSP00000380448.4	O14791-1
APOL1	ENST00000319136.8	TSL:1	c.30-74_30-73delAA	intron	N/A	ENSP00000317674.4	O14791-2
APOL1	ENST00000438034.6	TSL:4	c.30-35_30-34delAA	intron	N/A	ENSP00000404525.2	B1AH94

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000158

AC:

AN:

1266340

Hom.:

AF XY:

0.00000158

AC XY:

AN XY:

631866

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29274

American (AMR)

AF:

0.00

AC:

AN:

39504

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22382

East Asian (EAS)

AF:

0.00

AC:

AN:

34100

South Asian (SAS)

AF:

0.00

AC:

AN:

76832

European-Finnish (FIN)

AF:

0.0000211

AC:

AN:

47354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4234

European-Non Finnish (NFE)

AF:

0.00000104

AC:

AN:

960342

Other (OTH)

AF:

0.00

AC:

AN:

52318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.19

BranchPoint Hunter

1.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over