NM_178127.5:c.346-25C>T

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

2

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]

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 HGVSp Effect Exon rank MANE Protein UniProt
ANGPTL5NM_178127.5 linkc.346-25C>T intron_variant Intron 4 of 8 ENST00000334289.7 NP_835228.2 Q86XS5
ANGPTL5XM_011542735.4 linkc.345+812C>T intron_variant Intron 4 of 6 XP_011541037.1
ANGPTL5XM_017017466.3 linkc.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
ANGPTL5ENST00000334289.7 linkc.346-25C>T intron_variant Intron 4 of 8 1 NM_178127.5 ENSP00000335255.3 Q86XS5
ANGPTL5ENST00000534527.1 linkc.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.:
32
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.:
23
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
0
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
0
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.:
32
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
0
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
0
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
12
DANN
Benign
0.86
PhyloP100
0.30
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs1661409; hg19: chr11-101775663; API