2-198269732-C-A

Variant names:

• chr2-198269732-C-A
• rs3977
• ENST00000625084.1:n.45-85563C>A

Variant summary

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

The ENST00000625084.1(PLCL1):​n.45-85563C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,984 control chromosomes in the GnomAD database, including 16,416 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 0.43 (16416 hom., cov: 31)
• Consequence: PLCL1 ENST00000625084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 12 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.858 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000625084.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	ENST00000625084.1	TSL:5	n.45-85563C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64642 AN: 151866 Hom.: 16403 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.879

Gnomad SAS AF: 0.621

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.426 AC: 64673 AN: 151984 Hom.: 16416 Cov.: 31 AF XY: 0.439 AC XY: 32588 AN XY: 74266

African (AFR) AF: 0.148 AC: 6132 AN: 41474

American (AMR) AF: 0.528 AC: 8061 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3470

East Asian (EAS) AF: 0.879 AC: 4528 AN: 5152

South Asian (SAS) AF: 0.622 AC: 2983 AN: 4796

European-Finnish (FIN) AF: 0.592 AC: 6251 AN: 10562

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.495 AC: 33655 AN: 67948

Other (OTH) AF: 0.412 AC: 869 AN: 2110

Alfa AF: 0.472 Hom.: 9036

Bravo AF: 0.410

Asia WGS AF: 0.659 AC: 2289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.88
PhyloP100		0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3977; hg19: chr2-199134456;