NM_003661.4:c.45-240G>T

Variant names:

• chr22-36256843-G-T
• rs136147
• NM_003661.4:c.45-240G>T

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.45-240G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,978 control chromosomes in the GnomAD database, including 20,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (20755 hom., cov: 32)
• Consequence: APOL1 NM_003661.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36

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=-0.91).
• BP6: Variant 22-36256843-G-T is Benign according to our data. Variant chr22-36256843-G-T is described in ClinVar as [Benign]. Clinvar id is 1259540.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL1	NM_003661.4	c.45-240G>T		intron_variant	Intron 2 of 5	ENST00000397278.8	NP_003652.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL1	ENST00000397278.8	c.45-240G>T		intron_variant	Intron 2 of 5	1	NM_003661.4	ENSP00000380448.4

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78743 AN: 151860 Hom.: 20741 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.499

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.499

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.518 AC: 78796 AN: 151978 Hom.: 20755 Cov.: 32 AF XY: 0.523 AC XY: 38878 AN XY: 74300

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.499

Gnomad4 EAS AF: 0.711

Gnomad4 SAS AF: 0.612

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.503

Alfa AF: 0.489 Hom.: 2297

Bravo AF: 0.528

Asia WGS AF: 0.676 AC: 2351 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.082
DANN	Benign	0.45

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: rs136147; hg19: chr22-36652889; COSMIC: COSV59868226;