rs12718464

chr11-116836685-G-Achr11-116836685-G-T

Variant summary

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

The NM_000039.3(APOA1):c.201-274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0471 in 152,320 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.047 (244 hom., cov: 34)
• Consequence: APOA1 NM_000039.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27

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=-0.84).
• BP6: Variant 11-116836685-G-A is Benign according to our data. Variant chr11-116836685-G-A is described in ClinVar as [Benign]. Clinvar id is 1284090.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-116836685-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOA1	NM_000039.3	c.201-274C>T		intron_variant		ENST00000236850.5
APOA1-AS	NR_126362.1	n.123+446G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOA1	ENST00000236850.5	c.201-274C>T		intron_variant		1	NM_000039.3	P1
APOA1-AS	ENST00000669664.1	n.74+446G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7194 AN: 152202 Hom.: 244 Cov.: 34

Gnomad AFR AF: 0.0121

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.0982

Gnomad EAS AF: 0.0491

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0425

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

GnomAD4 genome AF: 0.0471 AC: 7181 AN: 152320 Hom.: 244 Cov.: 34 AF XY: 0.0480 AC XY: 3577 AN XY: 74488

Gnomad4 AFR AF: 0.0121

Gnomad4 AMR AF: 0.0336

Gnomad4 ASJ AF: 0.0982

Gnomad4 EAS AF: 0.0491

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0756

Gnomad4 NFE AF: 0.0609

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0374 Hom.: 34

Bravo AF: 0.0426

Asia WGS AF: 0.0780 AC: 272 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

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.9
Dann	Benign	0.71

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: rs12718464; hg19: chr11-116707401;