rs2338545

Positions:

• chr2-28576908-A-G

Variant summary

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

The NM_153021.5(PLB1):​c.1434-1199A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,052 control chromosomes in the GnomAD database, including 12,303 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 0.37 (12303 hom., cov: 32)
• Consequence: PLB1 NM_153021.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLB1	NM_153021.5	c.1434-1199A>G		intron_variant		ENST00000327757.10	NP_694566.4
PLB1	NM_001170585.2	c.1467-1199A>G		intron_variant			NP_001164056.1
PLB1	NR_138141.2	n.593-1199A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLB1	ENST00000327757.10	c.1434-1199A>G		intron_variant		1	NM_153021.5	ENSP00000330442	P1

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55830 AN: 151934 Hom.: 12276 Cov.: 32

Gnomad AFR AF: 0.591

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.368 AC: 55901 AN: 152052 Hom.: 12303 Cov.: 32 AF XY: 0.370 AC XY: 27508 AN XY: 74334

Gnomad4 AFR AF: 0.591

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.343

Alfa AF: 0.261 Hom.: 8410

Bravo AF: 0.402

Asia WGS AF: 0.371 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2338545; hg19: chr2-28799775;