rs9610474

Variant names:

• chr22-36266340-T-C
• rs9610474
• NM_003661.4:c.*307T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.53
• Publications: 7 publications found

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]

APOL1 Gene-Disease associations (from GenCC):

• focal segmental glomerulosclerosis 4, susceptibility to

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1248991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
APOL1	NM_003661.4	c.*307T>C		3_prime_UTR_variant	Exon 6 of 6	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8	c.*307T>C		3_prime_UTR_variant	Exon 6 of 6	1	NM_003661.4	ENSP00000380448.4

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

African (AFR) AF: 0.0295 AC: 207 AN: 7024

American (AMR) AF: 0.0924 AC: 874 AN: 9464

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 911 AN: 8940

East Asian (EAS) AF: 0.0222 AC: 495 AN: 22326

South Asian (SAS) AF: 0.132 AC: 1094 AN: 8314

European-Finnish (FIN) AF: 0.101 AC: 1906 AN: 18850

Middle Eastern (MID) AF: 0.131 AC: 164 AN: 1248

European-Non Finnish (NFE) AF: 0.142 AC: 22983 AN: 161980

Other (OTH) AF: 0.113 AC: 1847 AN: 16332

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

African (AFR) AF: 0.0296 AC: 1231 AN: 41536

American (AMR) AF: 0.107 AC: 1627 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 356 AN: 3470

East Asian (EAS) AF: 0.0292 AC: 150 AN: 5132

South Asian (SAS) AF: 0.131 AC: 631 AN: 4824

European-Finnish (FIN) AF: 0.0904 AC: 957 AN: 10586

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.153 AC: 10405 AN: 67896

Other (OTH) AF: 0.106 AC: 224 AN: 2108

Alfa AF: 0.128 Hom.: 190

Bravo AF: 0.0982

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.82
DANN	Benign	0.097
PhyloP100		-4.5
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: rs9610474; hg19: chr22-36662386;