rs7255436

Variant names:

• chr19-8368312-C-A
• rs7255436
• NM_139314.3:c.548-907C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139314.3(ANGPTL4):​c.548-907C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,912 control chromosomes in the GnomAD database, including 23,699 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 0.55 (23699 hom., cov: 31)
• Consequence: ANGPTL4 NM_139314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62
• Publications: 87 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.664 is higher than 0.05.

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.548-907C>A		intron	N/A	NP_647475.1	Q9BY76-1
	ANGPTL4	NM_001039667.3		c.547+1993C>A		intron	N/A	NP_001034756.1	Q9BY76-2
	ANGPTL4	NR_104213.2		n.596+2248C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANGPTL4	ENST00000301455.7	TSL:1 MANE Select	c.548-907C>A		intron	N/A	ENSP00000301455.1	Q9BY76-1
	ANGPTL4	ENST00000593998.5	TSL:1	n.548-907C>A		intron	N/A	ENSP00000472551.1	Q9BY76-1
	ANGPTL4	ENST00000955923.1		c.548-907C>A		intron	N/A	ENSP00000625982.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83032 AN: 151798 Hom.: 23668 Cov.: 31

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.0986

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.547 AC: 83122 AN: 151912 Hom.: 23699 Cov.: 31 AF XY: 0.543 AC XY: 40314 AN XY: 74240

African (AFR) AF: 0.671 AC: 27796 AN: 41434

American (AMR) AF: 0.490 AC: 7479 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2052 AN: 3470

East Asian (EAS) AF: 0.0992 AC: 511 AN: 5150

South Asian (SAS) AF: 0.507 AC: 2438 AN: 4812

European-Finnish (FIN) AF: 0.520 AC: 5484 AN: 10554

Middle Eastern (MID) AF: 0.497 AC: 144 AN: 290

European-Non Finnish (NFE) AF: 0.525 AC: 35662 AN: 67908

Other (OTH) AF: 0.546 AC: 1154 AN: 2112

Alfa AF: 0.521 Hom.: 64058

Bravo AF: 0.549

Asia WGS AF: 0.368 AC: 1282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.23
DANN	Benign	0.77
PhyloP100		-2.6
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: rs7255436; hg19: chr19-8433196;