rs2257104

Positions:

• chr6-143943803-C-A
• chr6-143943803-C-G

Variant summary

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

The NM_001317162.2(PLAGL1):​c.153-1140G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,020 control chromosomes in the GnomAD database, including 16,331 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 0.46 (16331 hom., cov: 32)
• Consequence: PLAGL1 NM_001317162.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLAGL1	NM_001317162.2	c.153-1140G>T		intron_variant		ENST00000674357.1	NP_001304091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLAGL1	ENST00000674357.1	c.153-1140G>T		intron_variant			NM_001317162.2	ENSP00000501459.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69688 AN: 151902 Hom.: 16309 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.550

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.459 AC: 69750 AN: 152020 Hom.: 16331 Cov.: 32 AF XY: 0.462 AC XY: 34338 AN XY: 74306

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.465

Alfa AF: 0.366 Hom.: 1859

Bravo AF: 0.463

Asia WGS AF: 0.600 AC: 2087 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	0.052
DANN	Benign	0.67

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: rs2257104; hg19: chr6-144264940; COSMIC: COSV61333704; COSMIC: COSV61333704;