rs1147169

Variant names:

• chr2-198036671-T-C
• rs1147169
• NM_006226.4:c.241-47087T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006226.4. 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
	PLCL1	NM_006226.4	MANE Select	c.241-47087T>C		intron	N/A	NP_006217.3	Q15111-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	ENST00000428675.6	TSL:1 MANE Select	c.241-47087T>C		intron	N/A	ENSP00000402861.1	Q15111-1
	PLCL1	ENST00000487695.6	TSL:5	c.19-47087T>C		intron	N/A	ENSP00000457588.1	H3BUD4
	PLCL1	ENST00000435320.1	TSL:2	n.*12+34663T>C		intron	N/A	ENSP00000410488.1	F8WAR2

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

African (AFR) AF: 0.679 AC: 28111 AN: 41424

American (AMR) AF: 0.643 AC: 9813 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2638 AN: 3468

East Asian (EAS) AF: 0.483 AC: 2493 AN: 5164

South Asian (SAS) AF: 0.689 AC: 3317 AN: 4814

European-Finnish (FIN) AF: 0.619 AC: 6526 AN: 10548

Middle Eastern (MID) AF: 0.861 AC: 253 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47106 AN: 67954

Other (OTH) AF: 0.713 AC: 1505 AN: 2112

Alfa AF: 0.696 Hom.: 49353

Bravo AF: 0.673

Asia WGS AF: 0.578 AC: 2014 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.70
PhyloP100		2.8
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: rs1147169; hg19: chr2-198901395;