11-116837537-C-T

Position:

• chr11-116837537-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000375323.5(APOA1):​c.-150G>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 0.00689 in 956,534 control chromosomes in the GnomAD database, including 49 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 0.0060 (11 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (38 hom.)
• Consequence: APOA1 ENST00000375323.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.006 (913/152272) while in subpopulation NFE AF= 0.00782 (532/68004). AF 95% confidence interval is 0.00727. There are 11 homozygotes in gnomad4. There are 417 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOA1	NM_000039.3	c.-21+68G>A		intron_variant		ENST00000236850.5	NP_000030.1
APOA1-AS	NR_126362.1	n.123+1298C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOA1	ENST00000236850.5	c.-21+68G>A		intron_variant		1	NM_000039.3	ENSP00000236850	P1
APOA1-AS	ENST00000669664.1	n.74+1298C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00600 AC: 913 AN: 152156 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.00101

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.00582

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00782

Gnomad OTH AF: 0.00957

GnomAD4 exome AF: 0.00706 AC: 5680 AN: 804262 Hom.: 38 Cov.: 11 AF XY: 0.00715 AC XY: 2938 AN XY: 410886

Gnomad4 AFR exome AF: 0.00104

Gnomad4 AMR exome AF: 0.00633

Gnomad4 ASJ exome AF: 0.0307

Gnomad4 EAS exome AF: 0.0000305

Gnomad4 SAS exome AF: 0.00161

Gnomad4 FIN exome AF: 0.00143

Gnomad4 NFE exome AF: 0.00798

Gnomad4 OTH exome AF: 0.00786

GnomAD4 genome AF: 0.00600 AC: 913 AN: 152272 Hom.: 11 Cov.: 33 AF XY: 0.00560 AC XY: 417 AN XY: 74446

Gnomad4 AFR AF: 0.00101

Gnomad4 AMR AF: 0.00582

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.00782

Gnomad4 OTH AF: 0.00947

Alfa AF: 0.00683 Hom.: 1

Bravo AF: 0.00685

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.068
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs1799837; hg19: chr11-116708253;