chr2-28510494-A-G

Variant names:

• chr2-28510494-A-G
• rs6748157
• NM_153021.5:c.56-6314A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153021.5(PLB1):​c.56-6314A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,968 control chromosomes in the GnomAD database, including 15,639 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 0.41 (15639 hom., cov: 31)
• Consequence: PLB1 NM_153021.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• Publications: 8 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153021.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLB1	NM_153021.5	MANE Select	c.56-6314A>G		intron	N/A	NP_694566.4
	PLB1	NM_001170585.2		c.56-6314A>G		intron	N/A	NP_001164056.1	Q6P1J6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLB1	ENST00000327757.10	TSL:1 MANE Select	c.56-6314A>G		intron	N/A	ENSP00000330442.5	Q6P1J6-1
	PLB1	ENST00000422425.6	TSL:1	c.56-6314A>G		intron	N/A	ENSP00000416440.2	Q6P1J6-3
	PLB1	ENST00000404858.5	TSL:1	c.50-6314A>G		intron	N/A	ENSP00000384187.1	H7BYX7

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62356 AN: 151850 Hom.: 15645 Cov.: 31

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.562

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.410 AC: 62333 AN: 151968 Hom.: 15639 Cov.: 31 AF XY: 0.407 AC XY: 30197 AN XY: 74282

African (AFR) AF: 0.138 AC: 5708 AN: 41434

American (AMR) AF: 0.378 AC: 5782 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2036 AN: 3464

East Asian (EAS) AF: 0.227 AC: 1173 AN: 5170

South Asian (SAS) AF: 0.430 AC: 2068 AN: 4814

European-Finnish (FIN) AF: 0.518 AC: 5463 AN: 10546

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.565 AC: 38419 AN: 67952

Other (OTH) AF: 0.469 AC: 988 AN: 2106

Alfa AF: 0.491 Hom.: 5035

Bravo AF: 0.383

Asia WGS AF: 0.315 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.59
PhyloP100		-0.064
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: rs6748157; hg19: chr2-28733361;