rs10424339

Variant names:

• chr19-44917236-G-A
• rs10424339
• NM_001645.5:c.194+911G>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+911G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 152,240 control chromosomes in the GnomAD database, including 324 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 0.036 (324 hom., cov: 31)
• Consequence: APOC1 NM_001645.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOC1	NM_001645.5	c.194+911G>A		intron_variant	Intron 3 of 3	ENST00000592535.6	NP_001636.1
APOC1	NM_001379687.1	c.339+766G>A		intron_variant	Intron 3 of 3		NP_001366616.1
APOC1	NM_001321065.2	c.194+911G>A		intron_variant	Intron 3 of 3		NP_001307994.1
APOC1	NM_001321066.2	c.194+911G>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.194+911G>A		intron_variant	Intron 3 of 3	1	NM_001645.5	ENSP00000468276.2

Frequencies

GnomAD3 genomes AF: 0.0359 AC: 5467 AN: 152122 Hom.: 323 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0360 AC: 5484 AN: 152240 Hom.: 324 Cov.: 31 AF XY: 0.0347 AC XY: 2581 AN XY: 74444

African (AFR) AF: 0.124 AC: 5170 AN: 41530

American (AMR) AF: 0.0154 AC: 235 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000323 AC: 22 AN: 68016

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0273 Hom.: 22

Bravo AF: 0.0408

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.48
PhyloP100		-0.62
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: rs10424339; hg19: chr19-45420493;