rs74544108

Positions:

• chr2-28552043-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_153021.5(PLB1):​c.1084-885G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0072 in 152,270 control chromosomes in the GnomAD database, including 18 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 0.0072 (18 hom., cov: 33)
• Consequence: PLB1 NM_153021.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

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=-0.9).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0072 (1097/152270) while in subpopulation AFR AF= 0.0251 (1045/41558). AF 95% confidence interval is 0.0239. There are 18 homozygotes in gnomad4. There are 518 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLB1	NM_153021.5	c.1084-885G>A		intron_variant		ENST00000327757.10
PLB1	NM_001170585.2	c.1117-885G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLB1	ENST00000327757.10	c.1084-885G>A		intron_variant		1	NM_153021.5	P1
PLB1	ENST00000404858.5	c.1113-885G>A		intron_variant		1
PLB1	ENST00000422425.6	c.1117-885G>A		intron_variant		1
PLB1	ENST00000436544.1	c.214-885G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.00719 AC: 1094 AN: 152152 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00575

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

GnomAD4 genome AF: 0.00720 AC: 1097 AN: 152270 Hom.: 18 Cov.: 33 AF XY: 0.00696 AC XY: 518 AN XY: 74462

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00479 Hom.: 0

Bravo AF: 0.00805

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.32
DANN	Benign	0.61

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: rs74544108; hg19: chr2-28774910;