rs5069

chr11-116837538-G-A

Variant summary

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

The ENST00000375323.5(APOA1):c.-151C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0498 in 950,756 control chromosomes in the GnomAD database, including 3,218 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1849 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1369 hom.)
• Consequence: APOA1 ENST00000375323.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.920

Genes affected

APOA1 (HGNC:600): (apolipoprotein A1) This gene encodes apolipoprotein A-I, which is the major protein component of high density lipoprotein (HDL) in plasma. The encoded preproprotein is proteolytically processed to generate the mature protein, which promotes cholesterol efflux from tissues to the liver for excretion, and is a cofactor for lecithin cholesterolacyltransferase (LCAT), an enzyme responsible for the formation of most plasma cholesteryl esters. This gene is closely linked with two other apolipoprotein genes on chromosome 11. Defects in this gene are associated with HDL deficiencies, including Tangier disease, and with systemic non-neuropathic amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein. [provided by RefSeq, Dec 2015]

APOA1-AS (HGNC:40079): (APOA1 antisense RNA)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-116837538-G-A is Benign according to our data. Variant chr11-116837538-G-A is described in ClinVar as [Benign]. Clinvar id is 1239868.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-116837538-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA1	NM_000039.3	c.-21+67C>T		intron_variant		ENST00000236850.5
APOA1-AS	NR_126362.1	n.123+1299G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA1	ENST00000236850.5	c.-21+67C>T		intron_variant		1	NM_000039.3	P1
APOA1-AS	ENST00000669664.1	n.74+1299G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.105 AC: 16021 AN: 152084 Hom.: 1849 Cov.: 32

Gnomad AFR AF: 0.292

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0465

Gnomad SAS AF: 0.0465

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0766

GnomAD4 exome AF: 0.0393 AC: 31355 AN: 798554 Hom.: 1369 Cov.: 10 AF XY: 0.0383 AC XY: 15621 AN XY: 408216

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.0333

Gnomad4 ASJ exome AF: 0.0260

Gnomad4 EAS exome AF: 0.0397

Gnomad4 SAS exome AF: 0.0454

Gnomad4 FIN exome AF: 0.0198

Gnomad4 NFE exome AF: 0.0314

Gnomad4 OTH exome AF: 0.0476

GnomAD4 genome AF: 0.105 AC: 16029 AN: 152202 Hom.: 1849 Cov.: 32 AF XY: 0.103 AC XY: 7699 AN XY: 74422

Gnomad4 AFR AF: 0.292

Gnomad4 AMR AF: 0.0506

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0464

Gnomad4 SAS AF: 0.0463

Gnomad4 FIN AF: 0.0165

Gnomad4 NFE AF: 0.0334

Gnomad4 OTH AF: 0.0753

Alfa AF: 0.0781 Hom.: 136

Bravo AF: 0.117

Asia WGS AF: 0.0580 AC: 200 AN: 3478

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

Sep 29, 2018

This variant is associated with the following publications: (PMID: 28924542, 8647374) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.45
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs5069; hg19: chr11-116708254;