rs34282181

Variant names:

• chr11-116791636-G-T
• rs34282181
• NM_001371904.1:c.111C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-116791636-G-T
• chr11-116791636-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001371904.1(APOA5):​c.111C>A​(p.Asp37Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00212 in 1,610,130 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.010 (29 hom., cov: 34)
  • Exomes 𝑓: 0.0012 (20 hom.)
• Consequence: APOA5 NM_001371904.1 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.673
• Publications: 12 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, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041744113).
• BP6: Variant 11-116791636-G-T is Benign according to our data. Variant chr11-116791636-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 496494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1597/152350) while in subpopulation AFR AF = 0.0368 (1528/41578). AF 95% confidence interval is 0.0352. There are 29 homozygotes in GnomAd4. There are 743 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1597 AD,SD gene.

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.111C>A	p.Asp37Glu	missense	Exon 2 of 3	NP_001358833.1	Q6Q788
	APOA5	NM_001166598.2		c.111C>A	p.Asp37Glu	missense	Exon 3 of 4	NP_001160070.1	A0A0B4RUS7
	APOA5	NM_052968.5		c.111C>A	p.Asp37Glu	missense	Exon 3 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.111C>A	p.Asp37Glu	missense	Exon 2 of 3	ENSP00000227665.4	Q6Q788
	APOA5	ENST00000433069.2	TSL:1	c.111C>A	p.Asp37Glu	missense	Exon 3 of 4	ENSP00000399701.2	Q6Q788
	APOA5	ENST00000673688.1		c.111C>A	p.Asp37Glu	missense	Exon 2 of 3	ENSP00000501141.1	A0A669KB69

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1595 AN: 152232 Hom.: 29 Cov.: 34

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00222

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00282 AC: 682 AN: 242240 AF XY: 0.00202

Gnomad AFR exome AF: 0.0362

Gnomad AMR exome AF: 0.00204

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000422

Gnomad OTH exome AF: 0.00117

GnomAD4 exome AF: 0.00125 AC: 1816 AN: 1457780 Hom.: 20 Cov.: 33 AF XY: 0.00111 AC XY: 806 AN XY: 724818

African (AFR) AF: 0.0369 AC: 1230 AN: 33360

American (AMR) AF: 0.00260 AC: 115 AN: 44292

Ashkenazi Jewish (ASJ) AF: 0.0000768 AC: 2 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39484

South Asian (SAS) AF: 0.0000702 AC: 6 AN: 85432

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53030

Middle Eastern (MID) AF: 0.00227 AC: 13 AN: 5724

European-Non Finnish (NFE) AF: 0.000254 AC: 282 AN: 1110186

Other (OTH) AF: 0.00277 AC: 167 AN: 60226

GnomAD4 genome AF: 0.0105 AC: 1597 AN: 152350 Hom.: 29 Cov.: 34 AF XY: 0.00997 AC XY: 743 AN XY: 74494

African (AFR) AF: 0.0368 AC: 1528 AN: 41578

American (AMR) AF: 0.00222 AC: 34 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000220 AC: 15 AN: 68032

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00393 Hom.: 19

Bravo AF: 0.0110

ESP6500AA AF: 0.0330 AC: 145

ESP6500EA AF: 0.000466 AC: 4

ExAC AF: 0.00325 AC: 394

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not provided (4)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0042	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.67
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.17
Sift	Benign	0.16	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.091		Gain of methylation at K38 (P = 0.0936)
MVP		0.87
MPC		0.45
ClinPred		0.0010	T
GERP RS		1.2
PromoterAI		-0.073	Neutral
Varity_R		0.048
gMVP		0.50
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34282181; hg19: chr11-116662352; COSMIC: COSV99068112; COSMIC: COSV99068112;