rs5750146

Variant names:

• chr22-35660681-G-A
• rs5750146
• NM_030641.4:c.*1085G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030641.4(APOL6):​c.*1085G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0869 in 152,704 control chromosomes in the GnomAD database, including 904 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 0.087 (903 hom., cov: 32)
  • Exomes 𝑓: 0.087 (1 hom.)
• Consequence: APOL6 NM_030641.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.545
• Publications: 2 publications found

Genes affected

APOL6 (HGNC:14870): (apolipoprotein L6) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL6	NM_030641.4	c.*1085G>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000409652.5	NP_085144.1
APOL6	XM_011530392.4	c.*1085G>A		3_prime_UTR_variant	Exon 4 of 4		XP_011528694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL6	ENST00000409652.5	c.*1085G>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_030641.4	ENSP00000386280.3

Frequencies

GnomAD3 genomes AF: 0.0868 AC: 13199 AN: 152148 Hom.: 895 Cov.: 32

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0598

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.0713

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0420

Gnomad OTH AF: 0.0840

GnomAD4 exome AF: 0.0868 AC: 38 AN: 438 Hom.: 1 Cov.: 0 AF XY: 0.112 AC XY: 24 AN XY: 214

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.0905 AC: 36 AN: 398

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0385 AC: 1 AN: 26

Other (OTH) AF: 0.100 AC: 1 AN: 10

GnomAD4 genome AF: 0.0869 AC: 13228 AN: 152266 Hom.: 903 Cov.: 32 AF XY: 0.0869 AC XY: 6466 AN XY: 74448

African (AFR) AF: 0.172 AC: 7130 AN: 41538

American (AMR) AF: 0.0597 AC: 914 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 379 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1006 AN: 5176

South Asian (SAS) AF: 0.0726 AC: 350 AN: 4824

European-Finnish (FIN) AF: 0.0368 AC: 390 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0420 AC: 2856 AN: 68028

Other (OTH) AF: 0.0846 AC: 179 AN: 2116

Alfa AF: 0.0573 Hom.: 1331

Bravo AF: 0.0917

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.23
PhyloP100		-0.55
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: rs5750146; hg19: chr22-36056728;