rs6000190

Variant names:

• chr22-36204795-A-C
• rs6000190
• ENST00000352371.5:c.-187T>G

Your query was ambiguous. Multiple possible variants found:

• chr22-36204795-A-C
• chr22-36204795-A-G

Variant summary

Our verdict is Likely benign. The variant received -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
• 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=-0.97).

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL4	ENST00000352371.5	c.-187T>G		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000338260.3
APOL4	ENST00000616056.4	c.-385T>G		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000483497.1
APOL4	ENST00000449084.2	n.14T>G		non_coding_transcript_exon_variant	Exon 1 of 4	5

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

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

African (AFR) AF: 0.000509 AC: 1 AN: 1966

American (AMR) AF: 0.00 AC: 0 AN: 2860

Ashkenazi Jewish (ASJ) AF: 0.000360 AC: 1 AN: 2774

East Asian (EAS) AF: 0.000372 AC: 2 AN: 5380

South Asian (SAS) AF: 0.00 AC: 0 AN: 5908

European-Finnish (FIN) AF: 0.000349 AC: 2 AN: 5736

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1984

European-Non Finnish (NFE) AF: 0.000111 AC: 5 AN: 45110

Other (OTH) AF: 0.000775 AC: 4 AN: 5160

⚠️ 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.: 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
PhyloP100		-1.9
PromoterAI		0.049	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: rs6000190; hg19: chr22-36600841;