rs12718464

Variant names:

• chr11-116836685-G-A
• rs12718464
• NM_000039.3:c.201-274C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-116836685-G-A
• chr11-116836685-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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 -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 VariationId is 1284090.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0936 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000039.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA1	NM_000039.3	MANE Select	c.201-274C>T		intron	N/A	NP_000030.1
	APOA1	NM_001318017.2		c.201-274C>T		intron	N/A	NP_001304946.1
	APOA1	NM_001318018.2		c.201-274C>T		intron	N/A	NP_001304947.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA1	ENST00000236850.5	TSL:1 MANE Select	c.201-274C>T		intron	N/A	ENSP00000236850.3
	APOA1	ENST00000375323.5	TSL:1	c.201-274C>T		intron	N/A	ENSP00000364472.1
	APOA1	ENST00000359492.6	TSL:2	c.201-274C>T		intron	N/A	ENSP00000352471.2

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

African (AFR) AF: 0.0121 AC: 502 AN: 41588

American (AMR) AF: 0.0336 AC: 514 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0982 AC: 341 AN: 3472

East Asian (EAS) AF: 0.0491 AC: 254 AN: 5178

South Asian (SAS) AF: 0.101 AC: 488 AN: 4832

European-Finnish (FIN) AF: 0.0756 AC: 802 AN: 10612

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.0609 AC: 4143 AN: 68016

Other (OTH) AF: 0.0421 AC: 89 AN: 2114

Alfa AF: 0.0473 Hom.: 68

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

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.71
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12718464; hg19: chr11-116707401;