rs781603527

Variant names:

• chr22-36253990-T-A
• rs781603527
• ENST00000319136.8:c.28T>A

Your query was ambiguous. Multiple possible variants found:

• chr22-36253990-T-A
• chr22-36253990-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145343.3(APOL1):​c.28T>A​(p.Leu10Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL1 NM_145343.3 missense, splice_region
• Scores: Splicing: ADA: 0.0001882
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10315636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4	c.-20+771T>A		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.-20+771T>A		intron_variant	Intron 1 of 5	1	NM_003661.4	ENSP00000380448.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.42
DANN	Benign	0.97
DEOGEN2	Benign	0.017	.;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.18	T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.060	N;N
REVEL	Benign	0.098
Sift	Benign	0.12	T;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.98	D;.
Vest4		0.17
MutPred		0.29		Gain of catalytic residue at L10 (P = 0.0308);Gain of catalytic residue at L10 (P = 0.0308);
MVP		0.067
MPC		0.30
ClinPred		0.33	T
GERP RS		-3.8
gMVP		0.052

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00019
dbscSNV1_RF	Benign	0.17
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: rs781603527; hg19: chr22-36650036;