rs7116797

Positions:

• chr11-116836622-A-G

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.201-211T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,208 control chromosomes in the GnomAD database, including 45,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.76 (45366 hom., cov: 34)
• Consequence: APOA1 NM_000039.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.226

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=-0.88).
• BP6: Variant 11-116836622-A-G is Benign according to our data. Variant chr11-116836622-A-G is described in ClinVar as [Benign]. Clinvar id is 1272681.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-116836622-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA1	NM_000039.3	c.201-211T>C		intron_variant		ENST00000236850.5	NP_000030.1
APOA1-AS	NR_126362.1	n.123+383A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA1	ENST00000236850.5	c.201-211T>C		intron_variant		1	NM_000039.3	ENSP00000236850	P1
APOA1-AS	ENST00000669664.1	n.74+383A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115172 AN: 152090 Hom.: 45349 Cov.: 34

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.640

Gnomad FIN AF: 0.857

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.757 AC: 115240 AN: 152208 Hom.: 45366 Cov.: 34 AF XY: 0.751 AC XY: 55894 AN XY: 74424

Gnomad4 AFR AF: 0.540

Gnomad4 AMR AF: 0.764

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.640

Gnomad4 FIN AF: 0.857

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.787

Alfa AF: 0.775 Hom.: 6708

Bravo AF: 0.747

Asia WGS AF: 0.619 AC: 2158 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	-0.88
CADD	Benign	8.4
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7116797; hg19: chr11-116707338;