22-36204690-A-T

Variant names:

• chr22-36204690-A-T
• rs5995250
• ENST00000352371.5:c.-82T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145660.2(APOL4):​c.-82T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000069 in 434,666 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: 30)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: APOL4 NM_145660.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145660.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL4	NM_145660.2		c.-82T>A		5_prime_UTR	Exon 1 of 5	NP_663693.1	Q9BPW4-1
	APOL4	NM_030643.4		c.-280T>A		5_prime_UTR	Exon 1 of 6	NP_085146.2	Q9BPW4-2
	APOL4	NM_145661.2		c.-280T>A		5_prime_UTR	Exon 1 of 6	NP_663694.1	Q9BRG6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL4	ENST00000352371.5	TSL:1	c.-82T>A		5_prime_UTR	Exon 1 of 5	ENSP00000338260.3	Q9BPW4-1
	APOL4	ENST00000616056.4	TSL:1	c.-280T>A		5_prime_UTR	Exon 1 of 6	ENSP00000483497.1	Q9BPW4-2
	APOL4	ENST00000397275.6	TSL:1	c.-280T>A		5_prime_UTR	Exon 1 of 6	ENSP00000380445.2	Q9BRG6

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000690 AC: 3 AN: 434666 Hom.: 0 Cov.: 6 AF XY: 0.00000875 AC XY: 2 AN XY: 228520

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

African (AFR) AF: 0.00 AC: 0 AN: 9606

American (AMR) AF: 0.00 AC: 0 AN: 17424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9448

East Asian (EAS) AF: 0.00 AC: 0 AN: 17280

South Asian (SAS) AF: 0.00 AC: 0 AN: 30784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3096

European-Non Finnish (NFE) AF: 0.00000979 AC: 3 AN: 306338

Other (OTH) AF: 0.00 AC: 0 AN: 20196

⚠️ 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.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.3
DANN	Benign	0.52
PhyloP100		-0.017
PromoterAI		0.12	Neutral

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: rs5995250; hg19: chr22-36600736;