rs1064725

Variant names:

• chr19-44919304-T-G
• rs1064725
• NM_001645.5:c.*74T>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.*74T>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 0.044 in 1,331,196 control chromosomes in the GnomAD database, including 1,708 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 0.034 (155 hom., cov: 32)
  • Exomes 𝑓: 0.045 (1553 hom.)
• Consequence: APOC1 NM_001645.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0590
• Publications: 30 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0744 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.*74T>G		3_prime_UTR	Exon 4 of 4	NP_001636.1
	APOC1	NM_001379687.1		c.*81T>G		3_prime_UTR	Exon 4 of 4	NP_001366616.1
	APOC1	NM_001321065.2		c.*74T>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.*74T>G		3_prime_UTR	Exon 4 of 4	ENSP00000468276.2
	APOC1	ENST00000588750.5	TSL:1	c.*74T>G		3_prime_UTR	Exon 5 of 5	ENSP00000465356.1
	APOC1	ENST00000588802.5	TSL:1	c.*74T>G		3_prime_UTR	Exon 4 of 4	ENSP00000468029.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5257 AN: 152134 Hom.: 156 Cov.: 32

Gnomad AFR AF: 0.00768

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0252

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0425

GnomAD4 exome AF: 0.0452 AC: 53298 AN: 1178944 Hom.: 1553 Cov.: 16 AF XY: 0.0472 AC XY: 28278 AN XY: 599250

African (AFR) AF: 0.00676 AC: 184 AN: 27206

American (AMR) AF: 0.0209 AC: 849 AN: 40604

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 1719 AN: 23484

East Asian (EAS) AF: 0.000209 AC: 8 AN: 38278

South Asian (SAS) AF: 0.0799 AC: 6331 AN: 79228

European-Finnish (FIN) AF: 0.0367 AC: 1908 AN: 51932

Middle Eastern (MID) AF: 0.0652 AC: 339 AN: 5202

European-Non Finnish (NFE) AF: 0.0462 AC: 39805 AN: 862092

Other (OTH) AF: 0.0423 AC: 2155 AN: 50918

GnomAD4 genome AF: 0.0345 AC: 5251 AN: 152252 Hom.: 155 Cov.: 32 AF XY: 0.0353 AC XY: 2631 AN XY: 74432

African (AFR) AF: 0.00765 AC: 318 AN: 41548

American (AMR) AF: 0.0251 AC: 384 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0811 AC: 391 AN: 4824

European-Finnish (FIN) AF: 0.0317 AC: 337 AN: 10620

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0501 AC: 3410 AN: 68006

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0452 Hom.: 285

Bravo AF: 0.0305

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.68
PhyloP100		0.059
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1064725; hg19: chr19-45422561; COSMIC: COSV52991540; COSMIC: COSV52991540;