rs5072

Positions:

• chr11-116836867-A-G
• chr11-116836867-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000236850.5(APOA1):​c.200+134T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.88 in 1,048,052 control chromosomes in the GnomAD database, including 409,572 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (59814 hom., cov: 32)
  • Exomes 𝑓: 0.88 (349758 hom.)
• Consequence: APOA1 ENST00000236850.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.42

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-116836867-A-G is Benign according to our data. Variant chr11-116836867-A-G is described in ClinVar as [Benign]. Clinvar id is 1220811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116836867-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA1	NM_000039.3	c.200+134T>C		intron_variant		ENST00000236850.5	NP_000030.1
APOA1-AS	NR_126362.1	n.123+628A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA1	ENST00000236850.5	c.200+134T>C		intron_variant		1	NM_000039.3	ENSP00000236850	P1
APOA1-AS	ENST00000669664.1	n.74+628A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.884 AC: 134450 AN: 152062 Hom.: 59777 Cov.: 32

Gnomad AFR AF: 0.907

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.821

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.873

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.878

GnomAD4 exome AF: 0.879 AC: 787669 AN: 895872 Hom.: 349758 AF XY: 0.872 AC XY: 402709 AN XY: 461568

Gnomad4 AFR exome AF: 0.901

Gnomad4 AMR exome AF: 0.801

Gnomad4 ASJ exome AF: 0.860

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.879

Gnomad4 NFE exome AF: 0.919

Gnomad4 OTH exome AF: 0.876

GnomAD4 genome AF: 0.884 AC: 134544 AN: 152180 Hom.: 59814 Cov.: 32 AF XY: 0.876 AC XY: 65152 AN XY: 74382

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.667

Gnomad4 SAS AF: 0.683

Gnomad4 FIN AF: 0.873

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.874

Alfa AF: 0.898 Hom.: 8022

Bravo AF: 0.888

Asia WGS AF: 0.682 AC: 2377 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.28
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5072; hg19: chr11-116707583;