rs4076317

Variant names:

• chr19-8364115-C-G
• rs4076317
• ENST00000599192.5:c.-116-91C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000599192.5. 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
	ANGPTL4	NM_139314.3	MANE Select	c.-207C>G		upstream_gene	N/A	NP_647475.1
	ANGPTL4	NM_001039667.3		c.-207C>G		upstream_gene	N/A	NP_001034756.1
	ANGPTL4	NR_104213.2		n.-40C>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL4	ENST00000599192.5	TSL:4	c.-116-91C>G		intron	N/A	ENSP00000473090.1
	ANGPTL4	ENST00000601886.1	TSL:5	c.-116-91C>G		intron	N/A	ENSP00000470307.1
	ANGPTL4	ENST00000601770.1	TSL:4	c.-116-91C>G		intron	N/A	ENSP00000471345.1

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

African (AFR) AF: 0.114 AC: 1301 AN: 11460

American (AMR) AF: 0.248 AC: 4121 AN: 16636

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 3653 AN: 12712

East Asian (EAS) AF: 0.215 AC: 6094 AN: 28392

South Asian (SAS) AF: 0.163 AC: 6614 AN: 40522

European-Finnish (FIN) AF: 0.321 AC: 8959 AN: 27912

Middle Eastern (MID) AF: 0.282 AC: 515 AN: 1826

European-Non Finnish (NFE) AF: 0.280 AC: 74010 AN: 264178

Other (OTH) AF: 0.257 AC: 6357 AN: 24722

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

African (AFR) AF: 0.130 AC: 5375 AN: 41378

American (AMR) AF: 0.284 AC: 4319 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1049 AN: 3464

East Asian (EAS) AF: 0.262 AC: 1338 AN: 5098

South Asian (SAS) AF: 0.187 AC: 893 AN: 4776

European-Finnish (FIN) AF: 0.347 AC: 3638 AN: 10490

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.293 AC: 19905 AN: 67820

Other (OTH) AF: 0.229 AC: 476 AN: 2082

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.7
DANN	Benign	0.69
PhyloP100		-0.52
PromoterAI		-0.0051	Neutral

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

Other links and lift over

dbSNP: rs4076317; hg19: chr19-8428999;