rs2268443

Positions:

• chr6-143951103-A-G
• chr6-143951103-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001317162.2(PLAGL1):​c.-324-2643T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 146,902 control chromosomes in the GnomAD database, including 19,878 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 0.48 (19878 hom., cov: 32)
• Consequence: PLAGL1 NM_001317162.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.28

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLAGL1	NM_001317162.2	c.-324-2643T>C		intron_variant		ENST00000674357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLAGL1	ENST00000674357.1	c.-324-2643T>C		intron_variant			NM_001317162.2	P1

Frequencies

GnomAD3 genomes AF: 0.479 AC: 70255 AN: 146784 Hom.: 19821 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.640

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.438

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.479 AC: 70371 AN: 146902 Hom.: 19878 Cov.: 32 AF XY: 0.486 AC XY: 34870 AN XY: 71740

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.445

Alfa AF: 0.341 Hom.: 7467

Bravo AF: 0.489

Asia WGS AF: 0.498 AC: 1732 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	14
DANN	Benign	0.82

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

LitVar

Other links and lift over

dbSNP: rs2268443; hg19: chr6-144272240;