rs1025818

Positions:

• chr3-16923529-T-C
• chr3-16923529-T-G

Variant summary

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

The NM_001144382.2(PLCL2):​c.327+38163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 152,086 control chromosomes in the GnomAD database, including 8,003 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 0.32 (8003 hom., cov: 32)
• Consequence: PLCL2 NM_001144382.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL2	NM_001144382.2	c.327+38163T>C		intron_variant		ENST00000615277.5	NP_001137854.1
PLCL2	XM_047447799.1	c.-13335T>C		5_prime_UTR_variant	1/7		XP_047303755.1
PLCL2	XM_006713073.4	c.12+23845T>C		intron_variant			XP_006713136.1
PLCL2	XM_017006025.2	c.-155-14026T>C		intron_variant			XP_016861514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL2	ENST00000615277.5	c.327+38163T>C		intron_variant		1	NM_001144382.2	ENSP00000478458
PLCL2	ENST00000460467.1	n.439-86145T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.316 AC: 48054 AN: 151966 Hom.: 8003 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.316 AC: 48059 AN: 152086 Hom.: 8003 Cov.: 32 AF XY: 0.320 AC XY: 23803 AN XY: 74356

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.525

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.315

Alfa AF: 0.337 Hom.: 9728

Bravo AF: 0.299

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1025818; hg19: chr3-16965021;