NM_030882.4:c.-133-1538A>G

Variant names:

• chr22-36234993-T-C
• rs2157249
• NM_030882.4:c.-133-1538A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

APOL2 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030882.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL2	NM_030882.4	MANE Select	c.-133-1538A>G		intron	N/A	NP_112092.2
	APOL2	NM_145637.3		c.-133-1538A>G		intron	N/A	NP_663612.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL2	ENST00000358502.10	TSL:1 MANE Select	c.-133-1538A>G		intron	N/A	ENSP00000351292.5
	APOL2	ENST00000249066.10	TSL:1	c.-133-1538A>G		intron	N/A	ENSP00000249066.6
	APOL2	ENST00000866483.1		c.-1671A>G		5_prime_UTR	Exon 1 of 4	ENSP00000536542.1

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

African (AFR) AF: 0.188 AC: 7786 AN: 41486

American (AMR) AF: 0.247 AC: 3775 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5182

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4820

European-Finnish (FIN) AF: 0.373 AC: 3944 AN: 10562

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24081 AN: 67952

Other (OTH) AF: 0.271 AC: 570 AN: 2106

Alfa AF: 0.329 Hom.: 14324

Bravo AF: 0.266

Asia WGS AF: 0.100 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.80
DANN	Benign	0.30
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2157249; hg19: chr22-36631039;