rs5114

Variant names:

• chr19-44915189-C-T
• rs5114
• NM_001645.5:c.58+240C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001645.5(APOC1):​c.58+240C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 568,182 control chromosomes in the GnomAD database, including 33 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 0.011 (23 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (10 hom.)
• Consequence: APOC1 NM_001645.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• 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]

ENSG00000280087 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1647/152198) while in subpopulation AFR AF = 0.0371 (1540/41526). AF 95% confidence interval is 0.0355. There are 23 homozygotes in GnomAd4. There are 783 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

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.58+240C>T		intron	N/A	NP_001636.1	P02654
	APOC1	NM_001379687.1		c.58+240C>T		intron	N/A	NP_001366616.1	K7EPF9
	APOC1	NM_001321065.2		c.58+240C>T		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.58+240C>T		intron	N/A	ENSP00000468276.2	P02654
	APOC1	ENST00000588750.5	TSL:1	c.58+240C>T		intron	N/A	ENSP00000465356.1	P02654
	APOC1	ENST00000588802.5	TSL:1	c.58+240C>T		intron	N/A	ENSP00000468029.1	P02654

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1645 AN: 152080 Hom.: 23 Cov.: 31

Gnomad AFR AF: 0.0371

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00374

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00436 AC: 261 AN: 59834 AF XY: 0.00407

Gnomad AFR exome AF: 0.0390

Gnomad AMR exome AF: 0.00137

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000252

Gnomad OTH exome AF: 0.000491

GnomAD4 exome AF: 0.00161 AC: 670 AN: 415984 Hom.: 10 Cov.: 3 AF XY: 0.00138 AC XY: 303 AN XY: 219758

African (AFR) AF: 0.0357 AC: 414 AN: 11608

American (AMR) AF: 0.00206 AC: 37 AN: 17990

Ashkenazi Jewish (ASJ) AF: 0.00855 AC: 109 AN: 12756

East Asian (EAS) AF: 0.00 AC: 0 AN: 28114

South Asian (SAS) AF: 0.0000226 AC: 1 AN: 44210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27468

Middle Eastern (MID) AF: 0.000566 AC: 1 AN: 1768

European-Non Finnish (NFE) AF: 0.000125 AC: 31 AN: 248258

Other (OTH) AF: 0.00323 AC: 77 AN: 23812

GnomAD4 genome AF: 0.0108 AC: 1647 AN: 152198 Hom.: 23 Cov.: 31 AF XY: 0.0105 AC XY: 783 AN XY: 74404

African (AFR) AF: 0.0371 AC: 1540 AN: 41526

American (AMR) AF: 0.00373 AC: 57 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68012

Other (OTH) AF: 0.00664 AC: 14 AN: 2110

Alfa AF: 0.00676 Hom.: 2

Bravo AF: 0.0118

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		0.051
PromoterAI		-0.082	Neutral
Mutation Taster		=100/0	polymorphism

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: rs5114; hg19: chr19-45418446;