11-116837697-C-T

Position:

• chr11-116837697-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001318021.1(APOA1):​c.-396G>A variant causes a 5 prime UTR 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 NM_001318021.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.304

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA1	NM_001318021.1	c.-396G>A		5_prime_UTR_variant	1/4		NP_001304950.1
APOA1-AS	NR_126362.1	n.123+1458C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA1-AS	ENST00000444200.1	n.123+1458C>T		intron_variant		4
APOA1-AS	ENST00000669664.1	n.74+1458C>T		intron_variant

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

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.207

Gnomad4 SAS exome AF: 0.195

Gnomad4 FIN exome AF: 0.189

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.182

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

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.182

Alfa AF: 0.0954 Hom.: 132

Bravo AF: 0.177

Asia WGS AF: 0.222 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs670; hg19: chr11-116708413;