rs12721054

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-44919330-A-C
• chr19-44919330-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001645.5(APOC1):​c.*100A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000432 in 926,988 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOC1	NM_001645.5	c.*100A>C		3_prime_UTR_variant	Exon 4 of 4	ENST00000592535.6	NP_001636.1
APOC1	NM_001379687.1	c.*107A>C		3_prime_UTR_variant	Exon 4 of 4		NP_001366616.1
APOC1	NM_001321065.2	c.*100A>C		3_prime_UTR_variant	Exon 4 of 4		NP_001307994.1
APOC1	NM_001321066.2	c.*100A>C		3_prime_UTR_variant	Exon 5 of 5		NP_001307995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC1	ENST00000592535.6	c.*100A>C		3_prime_UTR_variant	Exon 4 of 4	1	NM_001645.5	ENSP00000468276.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000432 AC: 4 AN: 926988 Hom.: 0 Cov.: 12 AF XY: 0.00000833 AC XY: 4 AN XY: 480474

African (AFR) AF: 0.00 AC: 0 AN: 22144

American (AMR) AF: 0.000106 AC: 4 AN: 37680

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 71412

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4590

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 642874

Other (OTH) AF: 0.00 AC: 0 AN: 42484

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 238

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	14
DANN	Benign	0.87
PhyloP100		0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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;