22-36204795-A-C

Position:

• chr22-36204795-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000352371.5(APOL4):​c.-187T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000195 in 76,878 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: APOL4 ENST00000352371.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

Genes affected

APOL4 (HGNC:14867): (apolipoprotein L4) This gene encodes a member of the apolipoprotein L family. The encoded protein 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2020]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL4	NM_030643.4	c.-385T>G		5_prime_UTR_variant	1/6		NP_085146.2
APOL4	NM_145660.2	c.-187T>G		5_prime_UTR_variant	1/5		NP_663693.1
APOL4	NM_145661.2	c.-385T>G		5_prime_UTR_variant	1/6		NP_663694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL4	ENST00000352371.5	c.-187T>G		5_prime_UTR_variant	1/5	1		ENSP00000338260	A2
APOL4	ENST00000616056.4	c.-385T>G		5_prime_UTR_variant	1/6	1		ENSP00000483497	P2
APOL4	ENST00000332987.5	c.-489T>G		5_prime_UTR_variant	1/5	2		ENSP00000333229	P2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.000195 AC: 15 AN: 76878 Hom.: 0 Cov.: 1 AF XY: 0.000221 AC XY: 9 AN XY: 40654

Gnomad4 AFR exome AF: 0.000509

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000360

Gnomad4 EAS exome AF: 0.000372

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000349

Gnomad4 NFE exome AF: 0.000111

Gnomad4 OTH exome AF: 0.000775

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-36600841;