rs1372072

Positions:

• chr3-16913767-G-A
• chr3-16913767-G-C

Variant summary

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

The NM_001144382.2(PLCL2):​c.327+28401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,804 control chromosomes in the GnomAD database, including 9,431 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 0.35 (9431 hom., cov: 31)
• Consequence: PLCL2 NM_001144382.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559

Genes affected

PLCL2 (HGNC:9064): (phospholipase C like 2) Enables GABA receptor binding activity. Predicted to be involved in negative regulation of cold-induced thermogenesis and phosphatidylinositol-mediated signaling. Predicted to act upstream of or within several processes, including B cell activation; gamma-aminobutyric acid signaling pathway; and negative regulation of B cell receptor signaling pathway. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL2	NM_001144382.2	c.327+28401G>A		intron_variant		ENST00000615277.5	NP_001137854.1
PLCL2	XM_047447799.1	c.-23097G>A		5_prime_UTR_variant	1/7		XP_047303755.1
PLCL2	XM_006713073.4	c.12+14083G>A		intron_variant			XP_006713136.1
PLCL2	XM_017006025.2	c.-156+14083G>A		intron_variant			XP_016861514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL2	ENST00000615277.5	c.327+28401G>A		intron_variant		1	NM_001144382.2	ENSP00000478458
PLCL2	ENST00000460467.1	n.439-95907G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52815 AN: 151686 Hom.: 9425 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.439

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.348 AC: 52852 AN: 151804 Hom.: 9431 Cov.: 31 AF XY: 0.352 AC XY: 26140 AN XY: 74160

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.350

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.439

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.342

Alfa AF: 0.354 Hom.: 14190

Bravo AF: 0.335

Asia WGS AF: 0.431 AC: 1499 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.56
DANN	Benign	0.18

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1372072; hg19: chr3-16955259;