rs2280732

Variant names:

• chr2-28595500-T-G
• rs2280732
• ENST00000436544.1:c.*1447T>G

Variant summary

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

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PLB1	NM_153021.5	c.2321+1746T>G		intron_variant	Intron 33 of 57	ENST00000327757.10	NP_694566.4
PLB1	NM_001170585.2	c.2288+1746T>G		intron_variant	Intron 32 of 56		NP_001164056.1
PLB1	NR_138141.2	n.1414+1746T>G		intron_variant	Intron 13 of 35

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLB1	ENST00000436544.1	c.*1447T>G		3_prime_UTR_variant	Exon 21 of 21	1		ENSP00000392493.1
PLB1	ENST00000327757.10	c.2321+1746T>G		intron_variant	Intron 33 of 57	1	NM_153021.5	ENSP00000330442.5
PLB1	ENST00000422425.6	c.2288+1746T>G		intron_variant	Intron 32 of 56	1		ENSP00000416440.2
PLB1	ENST00000404858.5	c.2282+1746T>G		intron_variant	Intron 32 of 56	1		ENSP00000384187.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.119 AC: 4923 AN: 41464

American (AMR) AF: 0.167 AC: 2557 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 657 AN: 3468

East Asian (EAS) AF: 0.285 AC: 1473 AN: 5160

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4816

European-Finnish (FIN) AF: 0.253 AC: 2674 AN: 10552

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 12956 AN: 67980

Other (OTH) AF: 0.187 AC: 394 AN: 2108

Alfa AF: 0.185 Hom.: 1925

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
PhyloP100		-0.21
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: rs2280732; hg19: chr2-28818367;