rs10209501

chr2-28460510-G-Achr2-28460510-G-T

Variant summary

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

The ENST00000416713.5(PLB1):c.-114+3313G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 167,216 control chromosomes in the GnomAD database, including 6,097 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 0.25 (5560 hom., cov: 32)
  • Exomes 𝑓: 0.24 (537 hom.)
• Consequence: PLB1 ENST00000416713.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLB1	ENST00000416713.5	c.-114+3313G>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38735 AN: 151918 Hom.: 5566 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.378

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.265

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.243 AC: 3692 AN: 15180 Hom.: 537 AF XY: 0.243 AC XY: 2050 AN XY: 8442

Gnomad4 AFR exome AF: 0.0808

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.257

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.255 AC: 38732 AN: 152036 Hom.: 5560 Cov.: 32 AF XY: 0.252 AC XY: 18760 AN XY: 74328

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.378

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.265

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.273

Alfa AF: 0.294 Hom.: 901

Bravo AF: 0.241

Asia WGS AF: 0.232 AC: 807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	0.68
Dann	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10209501; hg19: chr2-28683377;