rs1147169

Positions:

• chr2-198036671-T-C

Variant summary

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

The NM_006226.4(PLCL1):​c.241-47087T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 151,958 control chromosomes in the GnomAD database, including 34,787 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 0.67 (34787 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.241-47087T>C		intron_variant		ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.19-47087T>C		intron_variant			XP_005246700.1
PLCL1	XM_017004339.3	c.3+34663T>C		intron_variant			XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.241-47087T>C		intron_variant		1	NM_006226.4	ENSP00000402861	P1
PLCL1	ENST00000487695.6	c.19-47087T>C		intron_variant		5		ENSP00000457588
PLCL1	ENST00000435320.1	c.*12+34663T>C		intron_variant, NMD_transcript_variant		2		ENSP00000410488

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102403 AN: 151838 Hom.: 34764 Cov.: 31

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.779

Gnomad AMR AF: 0.643

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.674 AC: 102471 AN: 151958 Hom.: 34787 Cov.: 31 AF XY: 0.673 AC XY: 49985 AN XY: 74252

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.643

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.689

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.713

Alfa AF: 0.699 Hom.: 38576

Bravo AF: 0.673

Asia WGS AF: 0.578 AC: 2014 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.70

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: rs1147169; hg19: chr2-198901395;