ENST00000444200.2:n.123+1458C>T

Variant names:

• chr11-116837697-C-T
• rs670
• ENST00000444200.2:n.123+1458C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000444200.2(APOA1-AS):​n.123+1458C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 563,690 control chromosomes in the GnomAD database, including 9,176 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.17 (2321 hom., cov: 32)
  • Exomes 𝑓: 0.18 (6855 hom.)
• Consequence: APOA1-AS ENST00000444200.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304
• Publications: 99 publications found

Genes affected

APOA1-AS (HGNC:40079): (APOA1 antisense RNA)

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 Gene-Disease associations (from GenCC):

• familial visceral amyloidosis

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hypoalphalipoproteinemia, primary, 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• AApoAI amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• apolipoprotein A-I deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444200.2. 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-AS	NR_126362.1		n.123+1458C>T		intron	N/A
	APOA1	NM_000039.3	MANE Select	c.-113G>A		upstream_gene	N/A	NP_000030.1
	APOA1	NM_001318017.2		c.-190G>A		upstream_gene	N/A	NP_001304946.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA1-AS	ENST00000444200.2	TSL:4	n.123+1458C>T		intron	N/A
	APOA1-AS	ENST00000669664.1		n.74+1458C>T		intron	N/A
	APOA1	ENST00000236850.5	TSL:1 MANE Select	c.-113G>A		upstream_gene	N/A	ENSP00000236850.3

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26172 AN: 152058 Hom.: 2310 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.177 AC: 72845 AN: 411514 Hom.: 6855 Cov.: 0 AF XY: 0.178 AC XY: 38205 AN XY: 214432

African (AFR) AF: 0.152 AC: 1805 AN: 11852

American (AMR) AF: 0.248 AC: 4048 AN: 16296

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 1930 AN: 13004

East Asian (EAS) AF: 0.207 AC: 6137 AN: 29698

South Asian (SAS) AF: 0.195 AC: 7010 AN: 35904

European-Finnish (FIN) AF: 0.189 AC: 5325 AN: 28208

Middle Eastern (MID) AF: 0.200 AC: 376 AN: 1878

European-Non Finnish (NFE) AF: 0.167 AC: 41782 AN: 250286

Other (OTH) AF: 0.182 AC: 4432 AN: 24388

GnomAD4 genome AF: 0.172 AC: 26224 AN: 152176 Hom.: 2321 Cov.: 32 AF XY: 0.174 AC XY: 12950 AN XY: 74392

African (AFR) AF: 0.150 AC: 6227 AN: 41512

American (AMR) AF: 0.220 AC: 3358 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3468

East Asian (EAS) AF: 0.254 AC: 1315 AN: 5182

South Asian (SAS) AF: 0.202 AC: 976 AN: 4822

European-Finnish (FIN) AF: 0.190 AC: 2016 AN: 10604

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11254 AN: 67984

Other (OTH) AF: 0.182 AC: 383 AN: 2108

Alfa AF: 0.163 Hom.: 3077

Bravo AF: 0.177

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.44
PhyloP100		-0.30
PromoterAI		-0.061	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs670; hg19: chr11-116708413;