chr19-44919589-G-A

Variant names:

• chr19-44919589-G-A
• rs56131196
• NM_001645.5:c.*359G>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.*359G>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 152,130 control chromosomes in the GnomAD database, including 2,537 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 0.18 (2537 hom., cov: 31)
• Consequence: APOC1 NM_001645.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339
• Publications: 78 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001645.5. 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
	APOC1	NM_001645.5	MANE Select	c.*359G>A		downstream_gene	N/A	NP_001636.1
	APOC1	NM_001379687.1		c.*366G>A		downstream_gene	N/A	NP_001366616.1
	APOC1	NM_001321065.2		c.*359G>A		downstream_gene	N/A	NP_001307994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC1	ENST00000592535.6	TSL:1 MANE Select	c.*359G>A		downstream_gene	N/A	ENSP00000468276.2
	APOC1	ENST00000588750.5	TSL:1	c.*359G>A		downstream_gene	N/A	ENSP00000465356.1
	APOC1	ENST00000588802.5	TSL:1	c.*359G>A		downstream_gene	N/A	ENSP00000468029.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27108 AN: 152012 Hom.: 2528 Cov.: 31

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.179 AC: 27161 AN: 152130 Hom.: 2537 Cov.: 31 AF XY: 0.185 AC XY: 13729 AN XY: 74354

African (AFR) AF: 0.200 AC: 8281 AN: 41504

American (AMR) AF: 0.109 AC: 1668 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3470

East Asian (EAS) AF: 0.114 AC: 588 AN: 5176

South Asian (SAS) AF: 0.130 AC: 626 AN: 4826

European-Finnish (FIN) AF: 0.292 AC: 3087 AN: 10580

Middle Eastern (MID) AF: 0.151 AC: 44 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11873 AN: 67986

Other (OTH) AF: 0.140 AC: 295 AN: 2112

Alfa AF: 0.173 Hom.: 3569

Bravo AF: 0.166

Asia WGS AF: 0.178 AC: 622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.9
DANN	Benign	0.53
PhyloP100		0.34

Splicing

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

Other links and lift over

dbSNP: rs56131196; hg19: chr19-45422846;