rs389261

chr19-44917086-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC1	NM_001645.5	c.194+761G>A		intron_variant		ENST00000592535.6
APOC1	NM_001321065.2	c.194+761G>A		intron_variant
APOC1	NM_001321066.2	c.194+761G>A		intron_variant
APOC1	NM_001379687.1	c.339+616G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC1	ENST00000592535.6	c.194+761G>A		intron_variant		1	NM_001645.5	P1

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

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.0345

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0524 Hom.: 147

Bravo AF: 0.0854

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.88
Dann	Benign	0.35

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: rs389261; hg19: chr19-45420343;