2-197945251-G-A

Variant names:

• chr2-197945251-G-A
• rs1518364
• NM_006226.4:c.241-138507G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006226.4(PLCL1):​c.241-138507G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 151,874 control chromosomes in the GnomAD database, including 18,165 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 0.48 (18165 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	NM_006226.4	MANE Select	c.241-138507G>A		intron	N/A	NP_006217.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	ENST00000428675.6	TSL:1 MANE Select	c.241-138507G>A		intron	N/A	ENSP00000402861.1
	PLCL1	ENST00000487695.6	TSL:5	c.18+134929G>A		intron	N/A	ENSP00000457588.1
	PLCL1	ENST00000435320.1	TSL:2	n.241-56701G>A		intron	N/A	ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73419 AN: 151758 Hom.: 18171 Cov.: 31

Gnomad AFR AF: 0.551

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.484 AC: 73432 AN: 151874 Hom.: 18165 Cov.: 31 AF XY: 0.479 AC XY: 35581 AN XY: 74230

African (AFR) AF: 0.550 AC: 22759 AN: 41412

American (AMR) AF: 0.430 AC: 6558 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1707 AN: 3470

East Asian (EAS) AF: 0.226 AC: 1165 AN: 5146

South Asian (SAS) AF: 0.519 AC: 2497 AN: 4810

European-Finnish (FIN) AF: 0.392 AC: 4124 AN: 10516

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33012 AN: 67946

Other (OTH) AF: 0.498 AC: 1050 AN: 2108

Alfa AF: 0.491 Hom.: 58637

Bravo AF: 0.485

Asia WGS AF: 0.381 AC: 1328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.82
DANN	Benign	0.58
PhyloP100		-0.63
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: rs1518364; hg19: chr2-198809975; COSMIC: COSV70849939;