dbSNP rs2268447: PLAGL1:c.-325+3511A>G (chr6-143956958-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001317162.2(PLAGL1):c.-325+3511A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,114 control chromosomes in the GnomAD database, including 29,319 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 0.62 ( 29319 hom., cov: 33)

Consequence

PLAGL1
NM_001317162.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.788

Publications

3 publications found

Variant links:

Genes affected

PLAGL1 (HGNC:9046): (PLAG1 like zinc finger 1) This gene encodes a C2H2 zinc finger protein that functions as a suppressor of cell growth. This gene is often deleted or methylated and silenced in cancer cells. In addition, overexpression of this gene during fetal development is thought to be the causal factor for transient neonatal diabetes mellitus (TNDM). Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding two different protein isoforms. The P1 downstream promoter of this gene is imprinted, with preferential expression from the paternal allele in many tissues. [provided by RefSeq, Nov 2015]

PLAGL1 Gene-Disease associations (from GenCC):

transient neonatal diabetes mellitus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PLAGL1 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=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317162.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLAGL1	NM_001317162.2	MANE Select	c.-325+3511A>G	intron	N/A	NP_001304091.1
PLAGL1	NM_001080951.3		c.-325+3511A>G	intron	N/A	NP_001074420.1
PLAGL1	NM_001080952.3		c.-325+3511A>G	intron	N/A	NP_001074421.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PLAGL1	ENST00000674357.1	MANE Select	c.-325+3511A>G	intron	N/A	ENSP00000501459.1
PLAGL1	ENST00000354765.6	TSL:1	c.-325+3511A>G	intron	N/A	ENSP00000346810.2
PLAGL1	ENST00000367571.3	TSL:1	c.-325+3511A>G	intron	N/A	ENSP00000356543.1

Frequencies

GnomAD3 genomes

AF:

0.616

AC:

93569

AN:

151996

Hom.:

29306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.496

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.573

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.696

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.686

Gnomad OTH

AF:

0.640

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.615

AC:

93620

AN:

152114

Hom.:

29319

Cov.:

AF XY:

0.613

AC XY:

45607

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.496

AC:

20589

AN:

41498

American (AMR)

AF:

0.572

AC:

8751

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

2295

AN:

3468

East Asian (EAS)

AF:

0.619

AC:

3190

AN:

5154

South Asian (SAS)

AF:

0.560

AC:

2696

AN:

4818

European-Finnish (FIN)

AF:

0.696

AC:

7364

AN:

10580

Middle Eastern (MID)

AF:

0.609

AC:

179

AN:

294

European-Non Finnish (NFE)

AF:

0.686

AC:

46644

AN:

67992

Other (OTH)

AF:

0.641

AC:

1357

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1852

3705

5557

7410

9262

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.657

Hom.:

79541

Bravo

AF:

0.605

Asia WGS

AF:

0.601

AC:

2090

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

1.3

(source)

DANN

Benign

0.39

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over