rs12721046

Variant names:

• chr19-44917997-G-A
• rs12721046
• NM_001645.5:c.195-1176G>A

Variant summary

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

The NM_001645.5(APOC1):​c.195-1176G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 150,852 control chromosomes in the GnomAD database, including 1,267 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 0.11 (1267 hom., cov: 29)
• Consequence: APOC1 NM_001645.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 53 publications found

Genes affected

APOC1 (HGNC:607): (apolipoprotein C1) This gene encodes a member of the apolipoprotein C1 family. This gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. The encoded protein plays a central role in high density lipoprotein (HDL) and very low density lipoprotein (VLDL) metabolism. This protein has also been shown to inhibit cholesteryl ester transfer protein in plasma. A pseudogene of this gene is located 4 kb downstream in the same orientation, on the same chromosome. This gene is mapped to chromosome 19, where it resides within a apolipoprotein gene cluster. Alternative splicing and the use of alternative promoters results in multiple transcript variants. [provided by RefSeq, Sep 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOC1	NM_001645.5	c.195-1176G>A		intron_variant	Intron 3 of 3	ENST00000592535.6	NP_001636.1
APOC1	NM_001379687.1	c.340-1176G>A		intron_variant	Intron 3 of 3		NP_001366616.1
APOC1	NM_001321065.2	c.195-1176G>A		intron_variant	Intron 3 of 3		NP_001307994.1
APOC1	NM_001321066.2	c.195-1176G>A		intron_variant	Intron 4 of 4		NP_001307995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC1	ENST00000592535.6	c.195-1176G>A		intron_variant	Intron 3 of 3	1	NM_001645.5	ENSP00000468276.2

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16785 AN: 150732 Hom.: 1262 Cov.: 29

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.0788

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.0779

Gnomad NFE AF: 0.145

Gnomad OTH AF: 0.0831

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

GnomAD4 genome AF: 0.111 AC: 16809 AN: 150852 Hom.: 1267 Cov.: 29 AF XY: 0.118 AC XY: 8705 AN XY: 73666

African (AFR) AF: 0.0269 AC: 1103 AN: 41032

American (AMR) AF: 0.0794 AC: 1203 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3468

East Asian (EAS) AF: 0.113 AC: 564 AN: 5008

South Asian (SAS) AF: 0.103 AC: 494 AN: 4774

European-Finnish (FIN) AF: 0.274 AC: 2850 AN: 10388

Middle Eastern (MID) AF: 0.0868 AC: 25 AN: 288

European-Non Finnish (NFE) AF: 0.145 AC: 9810 AN: 67748

Other (OTH) AF: 0.0875 AC: 183 AN: 2092

Alfa AF: 0.0859 Hom.: 176

Bravo AF: 0.0936

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.38
DANN	Benign	0.92
PhyloP100		-2.3
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: rs12721046; hg19: chr19-45421254;