2-198220937-A-G

Position:

• chr2-198220937-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+71519A>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 0.798 in 152,020 control chromosomes in the GnomAD database, including 49,858 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 0.80 (49858 hom., cov: 32)
• Consequence: PLCL1 ENST00000625084.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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+71519A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121348 AN: 151902 Hom.: 49853 Cov.: 32

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.944

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.825

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

GnomAD4 genome AF: 0.798 AC: 121384 AN: 152020 Hom.: 49858 Cov.: 32 AF XY: 0.803 AC XY: 59664 AN XY: 74294

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.859

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.944

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.827

Alfa AF: 0.863 Hom.: 78404

Bravo AF: 0.787

Asia WGS AF: 0.939 AC: 3264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4850833; hg19: chr2-199085661;