rs992603

Positions:

• chr2-198162300-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000625084.1(PLCL1):​n.44+12882A>G variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000625084.1	n.44+12882A>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.941

Gnomad4 AMR AF: 0.916

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.889

Gnomad4 OTH AF: 0.915

Alfa AF: 0.902 Hom.: 59930

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs992603; hg19: chr2-199027024;