NM_001371904.1:c.49+55G>T

Variant names:

• chr11-116791757-C-A
• rs41338746
• NM_001371904.1:c.49+55G>T

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.49+55G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00856 in 1,613,600 control chromosomes in the GnomAD database, including 873 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (445 hom., cov: 34)
  • Exomes 𝑓: 0.0050 (428 hom.)
• Consequence: APOA5 NM_001371904.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.420
• Publications: 4 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-116791757-C-A is Benign according to our data. Variant chr11-116791757-C-A is described in ClinVar as Benign. ClinVar VariationId is 1252218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA5	NM_001371904.1	MANE Select	c.49+55G>T		intron	N/A	NP_001358833.1
	APOA5	NM_001166598.2		c.49+55G>T		intron	N/A	NP_001160070.1
	APOA5	NM_052968.5		c.49+55G>T		intron	N/A	NP_443200.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOA5	ENST00000227665.9	TSL:1 MANE Select	c.49+55G>T		intron	N/A	ENSP00000227665.4
	APOA5	ENST00000433069.2	TSL:1	c.49+55G>T		intron	N/A	ENSP00000399701.2
	APOA5	ENST00000673688.1		c.49+55G>T		intron	N/A	ENSP00000501141.1

Frequencies

GnomAD3 genomes AF: 0.0430 AC: 6537 AN: 152186 Hom.: 445 Cov.: 34

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.0335

GnomAD4 exome AF: 0.00497 AC: 7263 AN: 1461296 Hom.: 428 Cov.: 33 AF XY: 0.00444 AC XY: 3224 AN XY: 726920

African (AFR) AF: 0.159 AC: 5304 AN: 33458

American (AMR) AF: 0.00727 AC: 325 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.0168 AC: 440 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000336 AC: 29 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53350

Middle Eastern (MID) AF: 0.00971 AC: 56 AN: 5766

European-Non Finnish (NFE) AF: 0.000459 AC: 510 AN: 1111656

Other (OTH) AF: 0.00992 AC: 599 AN: 60378

GnomAD4 genome AF: 0.0430 AC: 6549 AN: 152304 Hom.: 445 Cov.: 34 AF XY: 0.0418 AC XY: 3112 AN XY: 74482

African (AFR) AF: 0.147 AC: 6111 AN: 41536

American (AMR) AF: 0.0165 AC: 252 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

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

European-Non Finnish (NFE) AF: 0.000779 AC: 53 AN: 68026

Other (OTH) AF: 0.0331 AC: 70 AN: 2114

Alfa AF: 0.0260 Hom.: 35

Bravo AF: 0.0506

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Apr 07, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.82
PhyloP100		-0.42
PromoterAI		-0.045	Neutral
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

Other links and lift over

dbSNP: rs41338746; hg19: chr11-116662473; COSMIC: COSV57064895; COSMIC: COSV57064895;