19-44919330-A-G

Variant names:

• chr19-44919330-A-G
• rs12721054
• NM_001645.5:c.*100A>G

Variant summary

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

The NM_001645.5(APOC1):​c.*100A>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 0.0081 in 1,079,144 control chromosomes in the GnomAD database, including 475 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 0.035 (326 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (149 hom.)
• Consequence: APOC1 NM_001645.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 37 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC1	NM_001645.5	MANE Select	c.*100A>G		3_prime_UTR	Exon 4 of 4	NP_001636.1
	APOC1	NM_001379687.1		c.*107A>G		3_prime_UTR	Exon 4 of 4	NP_001366616.1
	APOC1	NM_001321065.2		c.*100A>G		3_prime_UTR	Exon 4 of 4	NP_001307994.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC1	ENST00000592535.6	TSL:1 MANE Select	c.*100A>G		3_prime_UTR	Exon 4 of 4	ENSP00000468276.2
	APOC1	ENST00000588750.5	TSL:1	c.*100A>G		3_prime_UTR	Exon 5 of 5	ENSP00000465356.1
	APOC1	ENST00000588802.5	TSL:1	c.*100A>G		3_prime_UTR	Exon 4 of 4	ENSP00000468029.1

Frequencies

GnomAD3 genomes AF: 0.0348 AC: 5295 AN: 152060 Hom.: 323 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.0230

GnomAD4 exome AF: 0.00369 AC: 3423 AN: 926966 Hom.: 149 Cov.: 12 AF XY: 0.00310 AC XY: 1488 AN XY: 480460

African (AFR) AF: 0.118 AC: 2615 AN: 22130

American (AMR) AF: 0.00669 AC: 252 AN: 37678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20646

East Asian (EAS) AF: 0.00 AC: 0 AN: 37096

South Asian (SAS) AF: 0.000266 AC: 19 AN: 71412

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48062

Middle Eastern (MID) AF: 0.0137 AC: 63 AN: 4590

European-Non Finnish (NFE) AF: 0.000162 AC: 104 AN: 642870

Other (OTH) AF: 0.00871 AC: 370 AN: 42482

GnomAD4 genome AF: 0.0349 AC: 5314 AN: 152178 Hom.: 326 Cov.: 32 AF XY: 0.0341 AC XY: 2534 AN XY: 74382

African (AFR) AF: 0.122 AC: 5079 AN: 41512

American (AMR) AF: 0.0105 AC: 161 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000338 AC: 23 AN: 68002

Other (OTH) AF: 0.0228 AC: 48 AN: 2108

Alfa AF: 0.0166 Hom.: 238

Bravo AF: 0.0392

Asia WGS AF: 0.00953 AC: 33 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs12721054; hg19: chr19-45422587;