chr19-44945183-G-C

Position:

• chr19-44945183-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001646.3(APOC4):​c.262G>C​(p.Asp88His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOC4 NM_001646.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

Genes affected

APOC4 (HGNC:611): (apolipoprotein C4) This gene encodes a lipid-binding protein belonging to the apolipoprotein gene family. The protein is thought to play a role in lipid metabolism. Polymorphisms in this gene may influence circulating lipid levels and may be associated with coronary artery disease risk. This gene is present in a cluster with other related apolipoprotein genes on chromosome 19. Naturally occurring read-through transcription exists between this gene and the neighboring downstream apolipoprotein C-II (APOC2) gene. [provided by RefSeq, Mar 2011]

APOC4-APOC2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC4	NM_001646.3	c.262G>C	p.Asp88His	missense_variant	3/3	ENST00000592954.2
APOC4-APOC2	NR_037932.1	n.302G>C		non_coding_transcript_exon_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC4	ENST00000592954.2	c.262G>C	p.Asp88His	missense_variant	3/3	1	NM_001646.3	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461802 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727214

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.026
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.55	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.51	D
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.91	D;N;N;N
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.69
MutPred		0.30		Gain of helix (P = 0.0854);
MVP		0.61
ClinPred		0.74	D
GERP RS		1.4
Varity_R		0.10
gMVP		0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-45448440;