rs2278236

Positions:

• chr19-8366697-G-A
• chr19-8366697-G-C

Variant summary

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

The NM_139314.3(ANGPTL4):​c.547+378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,730 control chromosomes in the GnomAD database, including 18,603 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 0.49 (18603 hom., cov: 30)
• Consequence: ANGPTL4 NM_139314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.481

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANGPTL4	NM_139314.3	c.547+378G>A		intron_variant		ENST00000301455.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANGPTL4	ENST00000301455.7	c.547+378G>A		intron_variant		1	NM_139314.3	P1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73892 AN: 151612 Hom.: 18595 Cov.: 30

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.0809

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.504

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.487 AC: 73947 AN: 151730 Hom.: 18603 Cov.: 30 AF XY: 0.485 AC XY: 35986 AN XY: 74170

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.0815

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.520

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.502

Alfa AF: 0.508 Hom.: 25105

Bravo AF: 0.480

Asia WGS AF: 0.344 AC: 1196 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs2278236; hg19: chr19-8431581;