rs200197036

Variant names:

• chr19-8366196-TC-T
• rs200197036
• NM_139314.3:c.430-4delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_139314.3(ANGPTL4):​c.430-4delC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0021 in 1,614,004 control chromosomes in the GnomAD database, including 80 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (35 hom., cov: 31)
  • Exomes 𝑓: 0.0011 (45 hom.)
• Consequence: ANGPTL4 NM_139314.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.345
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 19-8366196-TC-T is Benign according to our data. Variant chr19-8366196-TC-T is described in ClinVar as Benign. ClinVar VariationId is 783818.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0117 (1776/152178) while in subpopulation AFR AF = 0.0416 (1727/41518). AF 95% confidence interval is 0.04. There are 35 homozygotes in GnomAd4. There are 862 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139314.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL4	NM_139314.3	MANE Select	c.430-4delC		splice_region intron	N/A	NP_647475.1	Q9BY76-1
	ANGPTL4	NM_001039667.3		c.430-4delC		splice_region intron	N/A	NP_001034756.1	Q9BY76-2
	ANGPTL4	NR_104213.2		n.596+134delC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL4	ENST00000301455.7	TSL:1 MANE Select	c.430-5delC		splice_region intron	N/A	ENSP00000301455.1	Q9BY76-1
	ANGPTL4	ENST00000593998.5	TSL:1	n.430-5delC		splice_region intron	N/A	ENSP00000472551.1	Q9BY76-1
	ANGPTL4	ENST00000955923.1		c.430-5delC		splice_region intron	N/A	ENSP00000625982.1

Frequencies

GnomAD3 genomes AF: 0.0117 AC: 1776 AN: 152060 Hom.: 35 Cov.: 31

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00210

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00287 AC: 721 AN: 251346 AF XY: 0.00226

Gnomad AFR exome AF: 0.0414

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.00111 AC: 1618 AN: 1461826 Hom.: 45 Cov.: 32 AF XY: 0.000989 AC XY: 719 AN XY: 727210

African (AFR) AF: 0.0437 AC: 1463 AN: 33480

American (AMR) AF: 0.00121 AC: 54 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53390

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111976

Other (OTH) AF: 0.00139 AC: 84 AN: 60394

GnomAD4 genome AF: 0.0117 AC: 1776 AN: 152178 Hom.: 35 Cov.: 31 AF XY: 0.0116 AC XY: 862 AN XY: 74422

African (AFR) AF: 0.0416 AC: 1727 AN: 41518

American (AMR) AF: 0.00209 AC: 32 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 67992

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00547 Hom.: 1

Bravo AF: 0.0126

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.34
Mutation Taster		=99/1	polymorphism

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: rs200197036; hg19: chr19-8431080;