chr11-116832955-G-T

Variant names:

• chr11-116832955-G-T
• rs4225
• NM_000040.3:c.*71G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000040.3(APOC3):​c.*71G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,606,286 control chromosomes in the GnomAD database, including 274,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (18615 hom., cov: 33)
  • Exomes 𝑓: 0.58 (256337 hom.)
• Consequence: APOC3 NM_000040.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.142

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-116832955-G-T is Benign according to our data. Variant chr11-116832955-G-T is described in ClinVar as [Benign]. Clinvar id is 1225805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-116832955-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOC3	NM_000040.3	c.*71G>T		3_prime_UTR_variant	Exon 4 of 4	ENST00000227667.8	NP_000031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOC3	ENST00000227667.8	c.*71G>T		3_prime_UTR_variant	Exon 4 of 4	1	NM_000040.3	ENSP00000227667.2
APOC3	ENST00000630701.1	c.*71G>T		3_prime_UTR_variant	Exon 3 of 3	1		ENSP00000486182.1
APOC3	ENST00000375345.3	c.*71G>T		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000364494.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68199 AN: 151968 Hom.: 18618 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.477

GnomAD4 exome AF: 0.579 AC: 841593 AN: 1454200 Hom.: 256337 Cov.: 30 AF XY: 0.572 AC XY: 414102 AN XY: 723704

Gnomad4 AFR exome AF: 0.136 AC: 4531 AN: 33270

Gnomad4 AMR exome AF: 0.432 AC: 19239 AN: 44560

Gnomad4 ASJ exome AF: 0.540 AC: 14091 AN: 26090

Gnomad4 EAS exome AF: 0.176 AC: 6969 AN: 39636

Gnomad4 SAS exome AF: 0.318 AC: 27333 AN: 85896

Gnomad4 FIN exome AF: 0.544 AC: 28459 AN: 52324

Gnomad4 NFE exome AF: 0.638 AC: 706178 AN: 1107454

Gnomad4 Remaining exome AF: 0.540 AC: 32407 AN: 60062

GnomAD4 genome AF: 0.448 AC: 68184 AN: 152086 Hom.: 18615 Cov.: 33 AF XY: 0.440 AC XY: 32704 AN XY: 74326

Gnomad4 AFR AF: 0.158 AC: 0.158181 AN: 0.158181

Gnomad4 AMR AF: 0.463 AC: 0.463123 AN: 0.463123

Gnomad4 ASJ AF: 0.545 AC: 0.545009 AN: 0.545009

Gnomad4 EAS AF: 0.203 AC: 0.202635 AN: 0.202635

Gnomad4 SAS AF: 0.300 AC: 0.299917 AN: 0.299917

Gnomad4 FIN AF: 0.540 AC: 0.539526 AN: 0.539526

Gnomad4 NFE AF: 0.627 AC: 0.626913 AN: 0.626913

Gnomad4 OTH AF: 0.471 AC: 0.470588 AN: 0.470588

Alfa AF: 0.479 Hom.: 2945

Bravo AF: 0.433

Asia WGS AF: 0.215 AC: 752 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30420299, 30782561, 27624799) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.2
DANN	Benign	0.76
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

Publications

LitVar

Other links and lift over

dbSNP: rs4225; hg19: chr11-116703671; COSMIC: COSV52635690; COSMIC: COSV52635690;