rs9610474

chr22-36266340-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003661.4(APOL1):c.*307T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 406,502 control chromosomes in the GnomAD database, including 3,212 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.10 (998 hom., cov: 31)
  • Exomes 𝑓: 0.12 (2214 hom.)
• Consequence: APOL1 NM_003661.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.53

Genes affected

APOL1 (HGNC:618): (apolipoprotein L1) This gene encodes a secreted high density lipoprotein which binds to apolipoprotein A-I. Apolipoprotein A-I is a relatively abundant plasma protein and is the major apoprotein of HDL. It is involved in the formation of most cholesteryl esters in plasma and also promotes efflux of cholesterol from cells. This apolipoprotein L family member 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. Several different transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 22-36266340-T-C is Benign according to our data. Variant chr22-36266340-T-C is described in ClinVar as [Benign]. Clinvar id is 1248991.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL1	NM_003661.4	c.*307T>C		3_prime_UTR_variant	6/6	ENST00000397278.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL1	ENST00000397278.8	c.*307T>C		3_prime_UTR_variant	6/6	1	NM_003661.4	A2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15726 AN: 151906 Hom.: 997 Cov.: 31

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0290

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0904

Gnomad MID AF: 0.121

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.120 AC: 30481 AN: 254478 Hom.: 2214 Cov.: 0 AF XY: 0.122 AC XY: 15855 AN XY: 130164

Gnomad4 AFR exome AF: 0.0295

Gnomad4 AMR exome AF: 0.0924

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0222

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.103 AC: 15723 AN: 152024 Hom.: 998 Cov.: 31 AF XY: 0.102 AC XY: 7572 AN XY: 74312

Gnomad4 AFR AF: 0.0296

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0292

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.0904

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.106

Alfa AF: 0.128 Hom.: 190

Bravo AF: 0.0982

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.82
Dann	Benign	0.097

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

LitVar

Other links and lift over

dbSNP: rs9610474; hg19: chr22-36662386;