rs389261

Variant names:

• chr19-44917086-G-A
• rs389261
• NM_001645.5:c.194+761G>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.194+761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 152,104 control chromosomes in the GnomAD database, including 1,409 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 0.075 (1409 hom., cov: 31)
• Consequence: APOC1 NM_001645.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC1	NM_001645.5	MANE Select	c.194+761G>A		intron	N/A	NP_001636.1	P02654
	APOC1	NM_001379687.1		c.339+616G>A		intron	N/A	NP_001366616.1	K7EPF9
	APOC1	NM_001321065.2		c.194+761G>A		intron	N/A	NP_001307994.1	P02654

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC1	ENST00000592535.6	TSL:1 MANE Select	c.194+761G>A		intron	N/A	ENSP00000468276.2	P02654
	APOC1	ENST00000588750.5	TSL:1	c.194+761G>A		intron	N/A	ENSP00000465356.1	P02654
	APOC1	ENST00000588802.5	TSL:1	c.194+761G>A		intron	N/A	ENSP00000468029.1	P02654

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11349 AN: 151990 Hom.: 1408 Cov.: 31

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0346

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0748 AC: 11379 AN: 152104 Hom.: 1409 Cov.: 31 AF XY: 0.0720 AC XY: 5353 AN XY: 74362

African (AFR) AF: 0.257 AC: 10650 AN: 41428

American (AMR) AF: 0.0345 AC: 527 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.00122 AC: 83 AN: 68022

Other (OTH) AF: 0.0492 AC: 104 AN: 2112

Alfa AF: 0.0661 Hom.: 188

Bravo AF: 0.0854

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.88
DANN	Benign	0.35
PhyloP100		-1.6
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: rs389261; hg19: chr19-45420343;