11-116830488-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_000040.3(APOC3):c.-13-82C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000733 in 1,479,862 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (6 hom.)
• Consequence: APOC3 NM_000040.3 intron
• Scores: Splicing: ADA: 0.00002654
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.729

Genes affected

APOC3 (HGNC:610): (apolipoprotein C3) This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 11-116830488-C-T is Benign according to our data. Variant chr11-116830488-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207973.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 525 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC3	NM_000040.3	c.-13-82C>T		intron_variant		ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOC3	ENST00000227667.8	c.-13-82C>T		intron_variant		1	NM_000040.3	P1

Frequencies

GnomAD3 genomes AF: 0.00345 AC: 525 AN: 152152 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000936 AC: 199 AN: 212714 Hom.: 2 AF XY: 0.000731 AC XY: 84 AN XY: 114904

Gnomad AFR exome AF: 0.0100

Gnomad AMR exome AF: 0.000466

Gnomad ASJ exome AF: 0.00459

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000727

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000213

Gnomad OTH exome AF: 0.000743

GnomAD4 exome AF: 0.000419 AC: 556 AN: 1327592 Hom.: 6 Cov.: 21 AF XY: 0.000391 AC XY: 260 AN XY: 664284

Gnomad4 AFR exome AF: 0.0105

Gnomad4 AMR exome AF: 0.000470

Gnomad4 ASJ exome AF: 0.00441

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000492

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000329

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.00347 AC: 528 AN: 152270 Hom.: 2 Cov.: 32 AF XY: 0.00337 AC XY: 251 AN XY: 74468

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000588

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.00205 Hom.: 0

Bravo AF: 0.00373

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 13, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	5.3
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs192830070; hg19: chr11-116701204;