2-198040190-A-G

Variant names:

• chr2-198040190-A-G
• rs2196176
• NM_006226.4:c.241-43568A>G

Variant summary

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

The NM_006226.4(PLCL1):​c.241-43568A>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
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 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.241-43568A>G		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.241-43568A>G		intron	N/A	ENSP00000402861.1
	PLCL1	ENST00000487695.6	TSL:5	c.19-43568A>G		intron	N/A	ENSP00000457588.1
	PLCL1	ENST00000435320.1	TSL:2	n.*12+38182A>G		intron	N/A	ENSP00000410488.1

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

African (AFR) AF: 0.717 AC: 29721 AN: 41432

American (AMR) AF: 0.646 AC: 9858 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2640 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2507 AN: 5166

South Asian (SAS) AF: 0.703 AC: 3385 AN: 4812

European-Finnish (FIN) AF: 0.618 AC: 6516 AN: 10550

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47153 AN: 67974

Other (OTH) AF: 0.723 AC: 1528 AN: 2112

Alfa AF: 0.704 Hom.: 62306

Bravo AF: 0.687

Asia WGS AF: 0.597 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.22
PhyloP100		-0.18
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: rs2196176; hg19: chr2-198904914;