rs2071522

Variant names:

• chr11-116826822-T-C
• rs2071522
• ENST00000814126.1:n.136-1343T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-116826822-T-C
• chr11-116826822-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000814126.1(ENSG00000305923):​n.136-1343T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 151,990 control chromosomes in the GnomAD database, including 22,602 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 0.53 (22602 hom., cov: 32)
• Consequence: ENSG00000305923 ENST00000814126.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 4 publications found

Genes affected

ENSG00000305923 (HGNC:):

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000814126.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000305923	ENST00000814126.1		n.136-1343T>C		intron	N/A
	APOC3	ENST00000863784.1		c.-396T>C		upstream_gene	N/A	ENSP00000533843.1
	APOC3	ENST00000863785.1		c.-332T>C		upstream_gene	N/A	ENSP00000533844.1

Frequencies

GnomAD3 genomes AF: 0.528 AC: 80254 AN: 151872 Hom.: 22604 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.553

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.528 AC: 80273 AN: 151990 Hom.: 22602 Cov.: 32 AF XY: 0.523 AC XY: 38875 AN XY: 74266

African (AFR) AF: 0.315 AC: 13069 AN: 41464

American (AMR) AF: 0.569 AC: 8685 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1942 AN: 3468

East Asian (EAS) AF: 0.615 AC: 3162 AN: 5144

South Asian (SAS) AF: 0.493 AC: 2372 AN: 4810

European-Finnish (FIN) AF: 0.588 AC: 6215 AN: 10566

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.631 AC: 42876 AN: 67960

Other (OTH) AF: 0.554 AC: 1167 AN: 2108

Alfa AF: 0.560 Hom.: 3250

Bravo AF: 0.526

Asia WGS AF: 0.538 AC: 1875 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.4
DANN	Benign	0.42
PhyloP100		-0.057

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2071522; hg19: chr11-116697538;