rs5114

chr19-44915189-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.62).
• 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC1	NM_001645.5	c.58+240C>T		intron_variant		ENST00000592535.6
APOC1	NM_001321065.2	c.58+240C>T		intron_variant
APOC1	NM_001321066.2	c.58+240C>T		intron_variant
APOC1	NM_001379687.1	c.58+240C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC1	ENST00000592535.6	c.58+240C>T		intron_variant		1	NM_001645.5	P1

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

GnomAD3 exomes AF: 0.00436 AC: 261 AN: 59834 Hom.: 3 AF XY: 0.00407 AC XY: 121 AN XY: 29756

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 SAS 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

Gnomad4 AFR exome AF: 0.0357

Gnomad4 AMR exome AF: 0.00206

Gnomad4 ASJ exome AF: 0.00855

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000226

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000125

Gnomad4 OTH exome AF: 0.00323

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

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.00886 Hom.: 2

Bravo AF: 0.0118

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
Cadd	Benign	15
Dann	Benign	0.86

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: rs5114; hg19: chr19-45418446;