Genetic Variant ANGPTL5:c.346-25C>T (chr11-101904932-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178127.5(ANGPTL5):c.346-25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,552,014 control chromosomes in the GnomAD database, including 127,279 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 0.34 ( 9735 hom., cov: 32)

Exomes 𝑓: 0.40 ( 117544 hom. )

Consequence

ANGPTL5
NM_178127.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.302

Publications

11 publications found

Variant links:

Genes affected

ANGPTL5 (HGNC:19705): (angiopoietin like 5) Predicted to be active in collagen-containing extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ANGPTL5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178127.5. 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
	ANGPTL5	NM_178127.5	MANE Select	c.346-25C>T		intron	N/A	NP_835228.2	Q86XS5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ANGPTL5	ENST00000334289.7	TSL:1 MANE Select	c.346-25C>T	intron	N/A	ENSP00000335255.3	Q86XS5
ANGPTL5	ENST00000953417.1		c.346-25C>T	intron	N/A	ENSP00000623476.1
ANGPTL5	ENST00000953418.1		c.346-25C>T	intron	N/A	ENSP00000623477.1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52305

AN:

151856

Hom.:

9740

Cov.:

show subpopulations

Gnomad AFR

AF:

0.214

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.457

Gnomad SAS

AF:

0.306

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.370

Gnomad NFE

AF:

0.424

Gnomad OTH

AF:

0.354

GnomAD2 exomes

AF:

0.368

AC:

91045

AN:

247238

AF XY:

0.375

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.265

Gnomad ASJ exome

AF:

0.443

Gnomad EAS exome

AF:

0.453

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.404

GnomAD4 exome

AF:

0.404

AC:

566082

AN:

1400040

Hom.:

117544

Cov.:

AF XY:

0.404

AC XY:

283003

AN XY:

700300

show subpopulations

African (AFR)

AF:

0.209

AC:

6709

AN:

32124

American (AMR)

AF:

0.270

AC:

12006

AN:

44534

Ashkenazi Jewish (ASJ)

AF:

0.443

AC:

11395

AN:

25722

East Asian (EAS)

AF:

0.481

AC:

18899

AN:

39288

South Asian (SAS)

AF:

0.319

AC:

27135

AN:

84940

European-Finnish (FIN)

AF:

0.364

AC:

19019

AN:

52192

Middle Eastern (MID)

AF:

0.408

AC:

2304

AN:

5650

European-Non Finnish (NFE)

AF:

0.421

AC:

445421

AN:

1057296

Other (OTH)

AF:

0.398

AC:

23194

AN:

58294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

15067

30135

45202

60270

75337

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13204

26408

39612

52816

66020

<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:

0.344

AC:

52300

AN:

151974

Hom.:

9735

Cov.:

AF XY:

0.338

AC XY:

25069

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.214

AC:

8868

AN:

41464

American (AMR)

AF:

0.292

AC:

4463

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1519

AN:

3470

East Asian (EAS)

AF:

0.459

AC:

2370

AN:

5162

South Asian (SAS)

AF:

0.306

AC:

1475

AN:

4822

European-Finnish (FIN)

AF:

0.350

AC:

3686

AN:

10540

Middle Eastern (MID)

AF:

0.371

AC:

109

AN:

294

European-Non Finnish (NFE)

AF:

0.424

AC:

28776

AN:

67930

Other (OTH)

AF:

0.349

AC:

736

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1678

3357

5035

6714

8392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.396

Hom.:

39866

Bravo

AF:

0.335

Asia WGS

AF:

0.301

AC:

1046

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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