rs992603

Variant names:

• chr2-198162300-A-G
• rs992603
• ENST00000625084.1:n.44+12882A>G

Variant summary

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

The ENST00000625084.1(PLCL1):​n.44+12882A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 152,268 control chromosomes in the GnomAD database, including 63,429 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 0.91 (63429 hom., cov: 33)
• Consequence: PLCL1 ENST00000625084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000625084.1	n.44+12882A>G		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138807 AN: 152150 Hom.: 63376 Cov.: 33

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.912 AC: 138917 AN: 152268 Hom.: 63429 Cov.: 33 AF XY: 0.913 AC XY: 67977 AN XY: 74438

African (AFR) AF: 0.941 AC: 39116 AN: 41574

American (AMR) AF: 0.916 AC: 14010 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3174 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5175 AN: 5182

South Asian (SAS) AF: 0.957 AC: 4617 AN: 4826

European-Finnish (FIN) AF: 0.881 AC: 9328 AN: 10588

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60482 AN: 68014

Other (OTH) AF: 0.915 AC: 1937 AN: 2116

Alfa AF: 0.903 Hom.: 79323

Bravo AF: 0.916

Asia WGS AF: 0.975 AC: 3388 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.58
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs992603; hg19: chr2-199027024;