rs1049846

Variant names:

• chr6-143940343-C-T
• rs1049846
• NM_001317162.2:c.*1081G>A

Variant summary

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

The NM_001317162.2(PLAGL1):​c.*1081G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 151,916 control chromosomes in the GnomAD database, including 9,842 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 0.36 (9842 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: PLAGL1 NM_001317162.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.171

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=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLAGL1	NM_001317162.2	c.*1081G>A		3_prime_UTR_variant	Exon 8 of 8	ENST00000674357.1	NP_001304091.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLAGL1	ENST00000674357	c.*1081G>A		3_prime_UTR_variant	Exon 8 of 8		NM_001317162.2	ENSP00000501459.1

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54178 AN: 151798 Hom.: 9837 Cov.: 33

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.334

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.357 AC: 54234 AN: 151916 Hom.: 9842 Cov.: 33 AF XY: 0.356 AC XY: 26415 AN XY: 74234

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.337

Alfa AF: 0.348 Hom.: 18733

Bravo AF: 0.358

Asia WGS AF: 0.366 AC: 1271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	14
DANN	Benign	0.49

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: rs1049846; hg19: chr6-144261480;