rs2257104

Variant names:

• chr6-143943803-C-A
• rs2257104
• NM_001317162.2:c.153-1140G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	NM_001317162.2	MANE Select	c.153-1140G>T		intron	N/A	NP_001304091.1
	PLAGL1	NM_001080951.3		c.153-1140G>T		intron	N/A	NP_001074420.1
	PLAGL1	NM_001080952.3		c.153-1140G>T		intron	N/A	NP_001074421.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLAGL1	ENST00000674357.1	MANE Select	c.153-1140G>T		intron	N/A	ENSP00000501459.1
	PLAGL1	ENST00000354765.6	TSL:1	c.153-1140G>T		intron	N/A	ENSP00000346810.2
	PLAGL1	ENST00000367571.3	TSL:1	c.153-1140G>T		intron	N/A	ENSP00000356543.1

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

African (AFR) AF: 0.446 AC: 18501 AN: 41442

American (AMR) AF: 0.543 AC: 8303 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3470

East Asian (EAS) AF: 0.692 AC: 3577 AN: 5170

South Asian (SAS) AF: 0.583 AC: 2812 AN: 4824

European-Finnish (FIN) AF: 0.380 AC: 4018 AN: 10560

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.437 AC: 29708 AN: 67968

Other (OTH) AF: 0.465 AC: 980 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.052
DANN	Benign	0.67
PhyloP100		-1.6
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

Other links and lift over

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