rs5069

Variant names:

• chr11-116837538-G-A
• rs5069
• ENST00000375323.5:c.-151C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-116837538-G-A
• chr11-116837538-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000375323.5(APOA1):​c.-151C>T variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.920
• Publications: 59 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1239868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
APOA1	NM_000039.3	c.-21+67C>T		intron_variant	Intron 1 of 3	ENST00000236850.5	NP_000030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOA1	ENST00000236850.5	c.-21+67C>T		intron_variant	Intron 1 of 3	1	NM_000039.3	ENSP00000236850.3

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

African (AFR) AF: 0.296 AC: 5770 AN: 19482

American (AMR) AF: 0.0333 AC: 1010 AN: 30296

Ashkenazi Jewish (ASJ) AF: 0.0260 AC: 470 AN: 18090

East Asian (EAS) AF: 0.0397 AC: 1303 AN: 32796

South Asian (SAS) AF: 0.0454 AC: 2724 AN: 59970

European-Finnish (FIN) AF: 0.0198 AC: 897 AN: 45246

Middle Eastern (MID) AF: 0.0252 AC: 108 AN: 4278

European-Non Finnish (NFE) AF: 0.0314 AC: 17268 AN: 550498

Other (OTH) AF: 0.0476 AC: 1805 AN: 37898

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

African (AFR) AF: 0.292 AC: 12107 AN: 41498

American (AMR) AF: 0.0506 AC: 774 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3472

East Asian (EAS) AF: 0.0464 AC: 240 AN: 5172

South Asian (SAS) AF: 0.0463 AC: 223 AN: 4818

European-Finnish (FIN) AF: 0.0165 AC: 175 AN: 10626

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0334 AC: 2273 AN: 68002

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-0.92
PromoterAI		-0.016	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5069; hg19: chr11-116708254;