chr11-116830488-C-T

Variant names:

• chr11-116830488-C-T
• rs192830070
• NM_000040.3:c.-13-82C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.729
• Publications: 0 publications found

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]

APOC3 Gene-Disease associations (from GenCC):

• cholesterol-ester transfer protein deficiency

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 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 VariationId is 1207973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 528 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000040.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	NM_000040.3	MANE Select	c.-13-82C>T		intron	N/A	NP_000031.1	A3KPE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOC3	ENST00000227667.8	TSL:1 MANE Select	c.-13-82C>T		intron	N/A	ENSP00000227667.2	P02656
	APOC3	ENST00000863804.1		c.-13-82C>T		intron	N/A	ENSP00000533863.1
	APOC3	ENST00000375345.3	TSL:5	c.-36-5C>T		splice_region intron	N/A	ENSP00000364494.1	B0YIW2

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

GnomAD2 exomes AF: 0.000936 AC: 199 AN: 212714 AF XY: 0.000731

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 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

African (AFR) AF: 0.0105 AC: 326 AN: 31002

American (AMR) AF: 0.000470 AC: 19 AN: 40388

Ashkenazi Jewish (ASJ) AF: 0.00441 AC: 110 AN: 24926

East Asian (EAS) AF: 0.00 AC: 0 AN: 38562

South Asian (SAS) AF: 0.0000492 AC: 4 AN: 81374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48360

Middle Eastern (MID) AF: 0.000187 AC: 1 AN: 5354

European-Non Finnish (NFE) AF: 0.0000329 AC: 33 AN: 1001700

Other (OTH) AF: 0.00113 AC: 63 AN: 55926

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

African (AFR) AF: 0.0118 AC: 491 AN: 41556

American (AMR) AF: 0.000719 AC: 11 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00576 AC: 20 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67990

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00223 Hom.: 0

Bravo AF: 0.00373

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.3
DANN	Benign	0.40
PhyloP100		-0.73
PromoterAI		-0.024	Neutral
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs192830070; hg19: chr11-116701204;