rs2280732

chr2-28595500-T-G

Variant summary

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

The ENST00000436544.1(PLB1):c.*1447T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,032 control chromosomes in the GnomAD database, including 2,542 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 0.18 (2542 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: PLB1 ENST00000436544.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

Genes affected

PLB1 (HGNC:30041): (phospholipase B1) This gene encodes a membrane-associated phospholipase that displays lysophospholipase and phospholipase A2 activities through removal of sn-1 and sn-2 fatty acids of glycerophospholipids. In addition, it displays lipase and retinyl ester hydrolase activities. The encoded protein is highly conserved and is composed of a large, glycosylated extracellular domain composed of four tandem homologous domains, followed by a hydrophobic segment that anchors the enzyme to the membrane and a short C-terminal cytoplasmic tail. This gene has been identified as a candidate rheumatoid arthritis risk gene. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLB1	NM_153021.5	c.2321+1746T>G		intron_variant		ENST00000327757.10
PLB1	NM_001170585.2	c.2288+1746T>G		intron_variant
PLB1	NR_138141.2	n.1414+1746T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLB1	ENST00000436544.1	c.*1447T>G		3_prime_UTR_variant	21/21	1
PLB1	ENST00000327757.10	c.2321+1746T>G		intron_variant		1	NM_153021.5	P1
PLB1	ENST00000404858.5	c.2284+1746T>G		intron_variant		1
PLB1	ENST00000422425.6	c.2288+1746T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26958 AN: 151912 Hom.: 2537 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.177 AC: 26984 AN: 152030 Hom.: 2542 Cov.: 31 AF XY: 0.182 AC XY: 13497 AN XY: 74302

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.167

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.187

Alfa AF: 0.180 Hom.: 909

Bravo AF: 0.170

Asia WGS AF: 0.239 AC: 830 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.9
Dann	Benign	0.54

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: rs2280732; hg19: chr2-28818367;