chr22-36234993-T-C

Position:

• chr22-36234993-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030882.4(APOL2):​c.-133-1538A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 152,064 control chromosomes in the GnomAD database, including 6,857 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6857 hom., cov: 32)
• Consequence: APOL2 NM_030882.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

Genes affected

APOL2 (HGNC:619): (apolipoprotein L2) This gene is a member of the apolipoprotein L gene family. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids or allow the binding of lipids to organelles. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL2	NM_030882.4	c.-133-1538A>G		intron_variant		ENST00000358502.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL2	ENST00000358502.10	c.-133-1538A>G		intron_variant		1	NM_030882.4	P2

Frequencies

GnomAD3 genomes AF: 0.283 AC: 42974 AN: 151946 Hom.: 6852 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.283 AC: 42981 AN: 152064 Hom.: 6857 Cov.: 32 AF XY: 0.284 AC XY: 21097 AN XY: 74336

Gnomad4 AFR AF: 0.188

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.271

Alfa AF: 0.335 Hom.: 11677

Bravo AF: 0.266

Asia WGS AF: 0.100 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.30
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2157249; hg19: chr22-36631039;