rs651821

Variant names:

• chr11-116791863-C-T
• rs651821
• NM_001371904.1:c.-3G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-116791863-C-T
• chr11-116791863-C-A

Variant summary

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

The NM_001371904.1(APOA5):​c.-3G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,614,018 control chromosomes in the GnomAD database, including 675,649 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (60477 hom., cov: 34)
  • Exomes 𝑓: 0.92 (615172 hom.)
• Consequence: APOA5 NM_001371904.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.137
• Publications: 209 publications found

Genes affected

APOA5 (HGNC:17288): (apolipoprotein A5) The protein encoded by this gene is an apolipoprotein that plays an important role in regulating the plasma triglyceride levels, a major risk factor for coronary artery disease. It is a component of high density lipoprotein and is highly similar to a rat protein that is upregulated in response to liver injury. Mutations in this gene have been associated with hypertriglyceridemia and hyperlipoproteinemia type 5. This gene is located proximal to the apolipoprotein gene cluster on chromosome 11q23. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Oct 2009]

APOA5 Gene-Disease associations (from GenCC):

• hypertriglyceridemia 1

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• hyperlipoproteinemia type V

  Inheritance: AD, SD Classification: STRONG Submitted by: Genomics England PanelApp, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 11-116791863-C-T is Benign according to our data. Variant chr11-116791863-C-T is described in ClinVar as Benign. ClinVar VariationId is 1284811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371904.1. 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
	APOA5	NM_001371904.1	MANE Select	c.-3G>A		5_prime_UTR	Exon 1 of 3	NP_001358833.1	Q6Q788
	APOA5	NM_001166598.2		c.-3G>A		5_prime_UTR	Exon 2 of 4	NP_001160070.1	A0A0B4RUS7
	APOA5	NM_052968.5		c.-3G>A		5_prime_UTR	Exon 2 of 4	NP_443200.2	Q6Q788

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA5	ENST00000227665.9	TSL:1 MANE Select	c.-3G>A		5_prime_UTR	Exon 1 of 3	ENSP00000227665.4	Q6Q788
	APOA5	ENST00000433069.2	TSL:1	c.-3G>A		5_prime_UTR	Exon 2 of 4	ENSP00000399701.2	Q6Q788
	APOA5	ENST00000873022.1		c.-3G>A		splice_region	Exon 2 of 4	ENSP00000543081.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135380 AN: 152184 Hom.: 60460 Cov.: 34

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.864

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.884

GnomAD2 exomes AF: 0.879 AC: 220186 AN: 250512 AF XY: 0.881

Gnomad AFR exome AF: 0.848

Gnomad AMR exome AF: 0.820

Gnomad ASJ exome AF: 0.899

Gnomad EAS exome AF: 0.715

Gnomad FIN exome AF: 0.918

Gnomad NFE exome AF: 0.934

Gnomad OTH exome AF: 0.901

GnomAD4 exome AF: 0.916 AC: 1338287 AN: 1461716 Hom.: 615172 Cov.: 57 AF XY: 0.913 AC XY: 663959 AN XY: 727154

African (AFR) AF: 0.842 AC: 28177 AN: 33470

American (AMR) AF: 0.825 AC: 36853 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.898 AC: 23479 AN: 26134

East Asian (EAS) AF: 0.679 AC: 26953 AN: 39688

South Asian (SAS) AF: 0.819 AC: 70637 AN: 86246

European-Finnish (FIN) AF: 0.918 AC: 49030 AN: 53390

Middle Eastern (MID) AF: 0.879 AC: 5072 AN: 5768

European-Non Finnish (NFE) AF: 0.939 AC: 1043694 AN: 1111932

Other (OTH) AF: 0.901 AC: 54392 AN: 60392

GnomAD4 genome AF: 0.889 AC: 135451 AN: 152302 Hom.: 60477 Cov.: 34 AF XY: 0.886 AC XY: 66012 AN XY: 74482

African (AFR) AF: 0.849 AC: 35271 AN: 41552

American (AMR) AF: 0.864 AC: 13218 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3114 AN: 3472

East Asian (EAS) AF: 0.699 AC: 3614 AN: 5168

South Asian (SAS) AF: 0.811 AC: 3920 AN: 4834

European-Finnish (FIN) AF: 0.920 AC: 9777 AN: 10622

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.934 AC: 63569 AN: 68032

Other (OTH) AF: 0.879 AC: 1857 AN: 2112

Alfa AF: 0.917 Hom.: 291021

Bravo AF: 0.884

Asia WGS AF: 0.766 AC: 2665 AN: 3478

EpiCase AF: 0.928

EpiControl AF: 0.927

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.4
DANN	Benign	0.76
PhyloP100		-0.14
PromoterAI		-0.022	Neutral
Mutation Taster		=300/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs651821;

hg19: chr11-116662579;

COSMIC: COSV57065156;

COSMIC: COSV57065156;