Genetic Variant NM_178127.5: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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ANGPTL5	NM_178127.5 link	c.346-25C>T	intron_variant	Intron 4 of 8	ENST00000334289.7	NP_835228.2	Q86XS5
ANGPTL5	XM_011542735.4 link	c.345+812C>T	intron_variant	Intron 4 of 6		XP_011541037.1
ANGPTL5	XM_017017466.3 link	c.241+2171C>T	intron_variant	Intron 3 of 4		XP_016872955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANGPTL5	ENST00000334289.7 link	c.346-25C>T		intron_variant	Intron 4 of 8	1	NM_178127.5	ENSP00000335255.3		Q86XS5
ANGPTL5	ENST00000534527.1 link	c.345+812C>T		intron_variant	Intron 3 of 4	3		ENSP00000433562.1		E9PKF7

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over