dbSNP rs34600793: ANGPTL4:c.548-3C>T (chr19-8369216-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_139314.3(ANGPTL4):c.548-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,608,750 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 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: 32)

Exomes 𝑓: 0.0011 ( 46 hom. )

Consequence

ANGPTL4
NM_139314.3 splice_region, intron

Scores

Splicing: ADA: 0.01186

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.24

Publications

0 publications found

Variant links:

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]

ANGPTL4 links:

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

RAB11B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 19-8369216-C-T is Benign according to our data. Variant chr19-8369216-C-T is described in ClinVar as Benign. ClinVar VariationId is 783819.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0116 (1772/152248) while in subpopulation AFR AF = 0.0415 (1724/41554). AF 95% confidence interval is 0.0399. There are 35 homozygotes in GnomAd4. There are 859 alleles in the male GnomAd4 subpopulation. Median coverage is 32. 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGPTL4	NM_139314.3	MANE Select	c.548-3C>T	splice_region intron	N/A	NP_647475.1	Q9BY76-1
ANGPTL4	NM_001039667.3		c.548-1840C>T	intron	N/A	NP_001034756.1	Q9BY76-2
ANGPTL4	NR_104213.2		n.596+3152C>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGPTL4	ENST00000301455.7	TSL:1 MANE Select	c.548-3C>T	splice_region intron	N/A	ENSP00000301455.1	Q9BY76-1
ANGPTL4	ENST00000593998.5	TSL:1	n.548-3C>T	splice_region intron	N/A	ENSP00000472551.1	Q9BY76-1
ANGPTL4	ENST00000955923.1		c.548-3C>T	splice_region intron	N/A	ENSP00000625982.1

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1772

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0416

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

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:

0.00527

GnomAD2 exomes

AF:

0.00288

AC:

704

AN:

244060

AF XY:

0.00228

show subpopulations

Gnomad AFR exome

AF:

0.0417

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000453

Gnomad OTH exome

AF:

0.000511

GnomAD4 exome

AF:

0.00111

AC:

1620

AN:

1456502

Hom.:

Cov.:

AF XY:

0.000994

AC XY:

720

AN XY:

724094

show subpopulations

African (AFR)

AF:

0.0438

AC:

1462

AN:

33388

American (AMR)

AF:

0.00124

AC:

AN:

44230

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25812

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

84852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53252

Middle Eastern (MID)

AF:

0.000893

AC:

AN:

4480

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1110730

Other (OTH)

AF:

0.00140

AC:

AN:

60124

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

158

237

316

395

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0116

AC:

1772

AN:

152248

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

859

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0415

AC:

1724

AN:

41554

American (AMR)

AF:

0.00203

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68020

Other (OTH)

AF:

0.00521

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

178

268

357

446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00523

Hom.:

Bravo

AF:

0.0126

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.5

(source)

DANN

Benign

0.77

PhyloP100

2.2

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.012

dbscSNV1_RF

Benign

0.23

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over