rs4076317

Positions:

• chr19-8364115-C-G
• chr19-8364115-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000599192.5(ANGPTL4):​c.-116-91C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 579,858 control chromosomes in the GnomAD database, including 21,202 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 0.25 (5068 hom., cov: 28)
  • Exomes 𝑓: 0.26 (16134 hom.)
• Consequence: ANGPTL4 ENST00000599192.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.519

Genes affected

ANGPTL4 (HGNC:16039): (angiopoietin like 4) This gene encodes a glycosylated, secreted protein containing a C-terminal fibrinogen domain. The encoded protein is induced by peroxisome proliferation activators and functions as a serum hormone that regulates glucose homeostasis, lipid metabolism, and insulin sensitivity. This protein can also act as an apoptosis survival factor for vascular endothelial cells and can prevent metastasis by inhibiting vascular growth and tumor cell invasion. The C-terminal domain may be proteolytically-cleaved from the full-length secreted protein. Decreased expression of this gene has been associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. This gene was previously referred to as ANGPTL2 but has been renamed ANGPTL4. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANGPTL4	NM_139314.3	c.-207C>G		upstream_gene_variant		ENST00000301455.7	NP_647475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPTL4	ENST00000301455.7	c.-207C>G		upstream_gene_variant		1	NM_139314.3	ENSP00000301455.1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37277 AN: 151382 Hom.: 5068 Cov.: 28

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.261 AC: 111624 AN: 428360 Hom.: 16134 Cov.: 5 AF XY: 0.258 AC XY: 57551 AN XY: 223492

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.287

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.321

Gnomad4 NFE exome AF: 0.280

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.246 AC: 37287 AN: 151498 Hom.: 5068 Cov.: 28 AF XY: 0.250 AC XY: 18471 AN XY: 74002

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.293

Gnomad4 OTH AF: 0.229

Alfa AF: 0.173 Hom.: 393

Bravo AF: 0.238

Asia WGS AF: 0.202 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4076317; hg19: chr19-8428999;