rs2196176

chr2-198040190-A-G

Variant summary

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

The NM_006226.4(PLCL1):c.241-43568A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,986 control chromosomes in the GnomAD database, including 36,011 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 0.69 (36011 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

Genes affected

PLCL1 (HGNC:9063): (phospholipase C like 1 (inactive)) Predicted to enable phospholipase C 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 gamma-aminobutyric acid signaling pathway; regulation of GABAergic synaptic transmission; and regulation of peptidyl-serine phosphorylation. Predicted to be located in cytoplasm and plasma membrane. [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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL1	NM_006226.4	c.241-43568A>G		intron_variant		ENST00000428675.6
PLCL1	XM_005246643.5	c.19-43568A>G		intron_variant
PLCL1	XM_017004339.3	c.3+38182A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL1	ENST00000428675.6	c.241-43568A>G		intron_variant		1	NM_006226.4	P1
PLCL1	ENST00000487695.6	c.19-43568A>G		intron_variant		5
PLCL1	ENST00000435320.1	c.*12+38182A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104194 AN: 151868 Hom.: 35981 Cov.: 31

Gnomad AFR AF: 0.717

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.686 AC: 104272 AN: 151986 Hom.: 36011 Cov.: 31 AF XY: 0.685 AC XY: 50876 AN XY: 74272

Gnomad4 AFR AF: 0.717

Gnomad4 AMR AF: 0.646

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.723

Alfa AF: 0.707 Hom.: 49082

Bravo AF: 0.687

Asia WGS AF: 0.597 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.4
Dann	Benign	0.22

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: rs2196176; hg19: chr2-198904914;