chr19-8373832-G-A

Variant names:

• chr19-8373832-G-A
• rs11672433
• NM_139314.3:c.1167G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The ENST00000301455.7(ANGPTL4):​c.1167G>A​(p.Pro389Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 1,613,792 control chromosomes in the GnomAD database, including 14,878 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.096 (960 hom., cov: 32)
  • Exomes 𝑓: 0.13 (13918 hom.)
• Consequence: ANGPTL4 ENST00000301455.7 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -4.08
• Publications: 26 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]

RAB11B-AS1 (HGNC:44178): (RAB11B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 19-8373832-G-A is Benign according to our data. Variant chr19-8373832-G-A is described in ClinVar as Benign. ClinVar VariationId is 3056777.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-4.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000301455.7. 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.1167G>A	p.Pro389Pro	synonymous	Exon 7 of 7	NP_647475.1
	ANGPTL4	NM_001039667.3		c.1053G>A	p.Pro351Pro	synonymous	Exon 6 of 6	NP_001034756.1
	ANGPTL4	NR_104213.2		n.597-361G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL4	ENST00000301455.7	TSL:1 MANE Select	c.1167G>A	p.Pro389Pro	synonymous	Exon 7 of 7	ENSP00000301455.1
	ANGPTL4	ENST00000593998.5	TSL:1	n.1167G>A		non_coding_transcript_exon	Exon 7 of 8	ENSP00000472551.1
	ANGPTL4	ENST00000393962.6	TSL:5	c.1053G>A	p.Pro351Pro	synonymous	Exon 6 of 6	ENSP00000377534.1

Frequencies

GnomAD3 genomes AF: 0.0959 AC: 14595 AN: 152132 Hom.: 960 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0798

Gnomad ASJ AF: 0.0956

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.0989

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.101

GnomAD2 exomes AF: 0.102 AC: 25700 AN: 251108 AF XY: 0.106

Gnomad AFR exome AF: 0.0239

Gnomad AMR exome AF: 0.0570

Gnomad ASJ exome AF: 0.0999

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.0983

Gnomad NFE exome AF: 0.146

Gnomad OTH exome AF: 0.116

GnomAD4 exome AF: 0.132 AC: 192252 AN: 1461542 Hom.: 13918 Cov.: 32 AF XY: 0.131 AC XY: 95507 AN XY: 727078

African (AFR) AF: 0.0229 AC: 765 AN: 33478

American (AMR) AF: 0.0586 AC: 2620 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0984 AC: 2572 AN: 26136

East Asian (EAS) AF: 0.000479 AC: 19 AN: 39700

South Asian (SAS) AF: 0.0977 AC: 8429 AN: 86254

European-Finnish (FIN) AF: 0.0995 AC: 5285 AN: 53100

Middle Eastern (MID) AF: 0.145 AC: 835 AN: 5760

European-Non Finnish (NFE) AF: 0.148 AC: 164762 AN: 1111998

Other (OTH) AF: 0.115 AC: 6965 AN: 60392

GnomAD4 genome AF: 0.0958 AC: 14587 AN: 152250 Hom.: 960 Cov.: 32 AF XY: 0.0938 AC XY: 6986 AN XY: 74438

African (AFR) AF: 0.0256 AC: 1064 AN: 41566

American (AMR) AF: 0.0796 AC: 1218 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0956 AC: 332 AN: 3472

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.0909 AC: 439 AN: 4828

European-Finnish (FIN) AF: 0.0989 AC: 1048 AN: 10598

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10068 AN: 67998

Other (OTH) AF: 0.100 AC: 212 AN: 2112

Alfa AF: 0.131 Hom.: 2544

Bravo AF: 0.0895

Asia WGS AF: 0.0350 AC: 122 AN: 3478

EpiCase AF: 0.140

EpiControl AF: 0.145

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ANGPTL4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.067
DANN	Benign	0.62
PhyloP100		-4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs11672433; hg19: chr19-8438716;