chr8-56187590-G-A

Variant summary

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

The NM_002655.3(PLAG1):​c.-321-8077C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 152,116 control chromosomes in the GnomAD database, including 3,802 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 0.21 ( 3802 hom., cov: 32)

Consequence

PLAG1
NM_002655.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

24 publications found
Variant links:
Genes affected
PLAG1 (HGNC:9045): (PLAG1 zinc finger) Pleomorphic adenoma gene 1 encodes a zinc finger protein with 2 putative nuclear localization signals. PLAG1, which is developmentally regulated, has been shown to be consistently rearranged in pleomorphic adenomas of the salivary glands. PLAG1 is activated by the reciprocal chromosomal translocations involving 8q12 in a subset of salivary gland pleomorphic adenomas. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
PLAG1 Gene-Disease associations (from GenCC):
  • silver-russell syndrome 4
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

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=-1.0).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PLAG1NM_002655.3 linkc.-321-8077C>T intron_variant Intron 1 of 4 ENST00000316981.8 NP_002646.2 Q6DJT9-1A0A024R7Z0
PLAG1NM_001114634.2 linkc.-216-16401C>T intron_variant Intron 1 of 3 NP_001108106.1 Q6DJT9-1A0A024R7Z0
PLAG1NM_001114635.2 linkc.-103-16401C>T intron_variant Intron 1 of 2 NP_001108107.1 Q6DJT9-2
PLAG1XM_017013576.2 linkc.-449-8077C>T intron_variant Intron 1 of 5 XP_016869065.1 Q6DJT9-1A0A024R7Z0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PLAG1ENST00000316981.8 linkc.-321-8077C>T intron_variant Intron 1 of 4 1 NM_002655.3 ENSP00000325546.3 Q6DJT9-1
PLAG1ENST00000429357.2 linkc.-216-16401C>T intron_variant Intron 1 of 3 1 ENSP00000416537.2 Q6DJT9-1
PLAG1ENST00000423799.6 linkc.-103-16401C>T intron_variant Intron 1 of 2 2 ENSP00000404067.2 Q6DJT9-2

Frequencies

GnomAD3 genomes
AF:
0.212
AC:
32273
AN:
151998
Hom.:
3781
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.306
Gnomad AMI
AF:
0.391
Gnomad AMR
AF:
0.179
Gnomad ASJ
AF:
0.279
Gnomad EAS
AF:
0.0731
Gnomad SAS
AF:
0.143
Gnomad FIN
AF:
0.146
Gnomad MID
AF:
0.209
Gnomad NFE
AF:
0.183
Gnomad OTH
AF:
0.224
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.213
AC:
32343
AN:
152116
Hom.:
3802
Cov.:
32
AF XY:
0.209
AC XY:
15508
AN XY:
74364
show subpopulations
African (AFR)
AF:
0.307
AC:
12708
AN:
41442
American (AMR)
AF:
0.179
AC:
2735
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.279
AC:
969
AN:
3472
East Asian (EAS)
AF:
0.0729
AC:
378
AN:
5186
South Asian (SAS)
AF:
0.143
AC:
688
AN:
4828
European-Finnish (FIN)
AF:
0.146
AC:
1545
AN:
10586
Middle Eastern (MID)
AF:
0.224
AC:
66
AN:
294
European-Non Finnish (NFE)
AF:
0.183
AC:
12431
AN:
67996
Other (OTH)
AF:
0.222
AC:
467
AN:
2106
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1279
2557
3836
5114
6393
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
332
664
996
1328
1660
<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:
0.193
Hom.:
13441
Bravo
AF:
0.219
Asia WGS
AF:
0.140
AC:
489
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.037
DANN
Benign
0.35
PhyloP100
-1.3
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

Publications

Other links and lift over

dbSNP: rs7833986; hg19: chr8-57100149; API