rs4420638

Variant names:

• chr19-44919689-A-G
• rs4420638
• ENST00000876409.1:c.*459A>G

Variant summary

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

The ENST00000876409.1(APOC1):​c.*459A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 151,786 control chromosomes in the GnomAD database, including 2,566 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.18 (2566 hom., cov: 31)
• Consequence: APOC1 ENST00000876409.1 3_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.31
• Publications: 541 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000876409.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC1	ENST00000876409.1		c.*459A>G		3_prime_UTR	Exon 7 of 7	ENSP00000546468.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27280 AN: 151670 Hom.: 2557 Cov.: 31

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.180 AC: 27333 AN: 151786 Hom.: 2566 Cov.: 31 AF XY: 0.186 AC XY: 13792 AN XY: 74186

African (AFR) AF: 0.204 AC: 8438 AN: 41374

American (AMR) AF: 0.110 AC: 1682 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 520 AN: 3468

East Asian (EAS) AF: 0.113 AC: 585 AN: 5160

South Asian (SAS) AF: 0.131 AC: 629 AN: 4812

European-Finnish (FIN) AF: 0.292 AC: 3070 AN: 10524

Middle Eastern (MID) AF: 0.154 AC: 45 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11884 AN: 67908

Other (OTH) AF: 0.143 AC: 301 AN: 2106

Alfa AF: 0.172 Hom.: 6776

Bravo AF: 0.168

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.48
DANN	Benign	0.59
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs4420638; hg19: chr19-45422946;