dbSNP rs1064725: APOC1:c.*74T>G (chr19-44919304-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0590

Variant links:

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]

APOC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
APOC1	NM_001645.5 link	c.*74T>G	3_prime_UTR_variant	Exon 4 of 4	ENST00000592535.6	NP_001636.1	P02654A0A024R0T8
APOC1	NM_001379687.1 link	c.*81T>G	3_prime_UTR_variant	Exon 4 of 4		NP_001366616.1
APOC1	NM_001321065.2 link	c.*74T>G	3_prime_UTR_variant	Exon 4 of 4		NP_001307994.1	P02654A0A024R0T8
APOC1	NM_001321066.2 link	c.*74T>G	3_prime_UTR_variant	Exon 5 of 5		NP_001307995.1	P02654A0A024R0T8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC1	ENST00000592535.6 link	c.*74T>G		3_prime_UTR_variant	Exon 4 of 4	1	NM_001645.5	ENSP00000468276.2		P02654K7ERI9

Frequencies

GnomAD3 genomes

AF:

0.0346

AC:

5257

AN:

152134

Hom.:

156

Cov.:

show subpopulations

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.:

AF XY:

0.0472

AC XY:

28278

AN XY:

599250

show subpopulations

Gnomad4 AFR exome

AF:

0.00676

Gnomad4 AMR exome

AF:

0.0209

Gnomad4 ASJ exome

AF:

0.0732

Gnomad4 EAS exome

AF:

0.000209

Gnomad4 SAS exome

AF:

0.0799

Gnomad4 FIN exome

AF:

0.0367

Gnomad4 NFE exome

AF:

0.0462

Gnomad4 OTH exome

AF:

0.0423

GnomAD4 genome

AF:

0.0345

AC:

5251

AN:

152252

Hom.:

155

Cov.:

AF XY:

0.0353

AC XY:

2631

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00765

Gnomad4 AMR

AF:

0.0251

Gnomad4 ASJ

AF:

0.0795

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0811

Gnomad4 FIN

AF:

0.0317

Gnomad4 NFE

AF:

0.0501

Gnomad4 OTH

AF:

0.0416

Alfa

AF:

0.0469

Hom.:

208

Bravo

AF:

0.0305

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over