2-198208610-T-C

Variant summary

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

The ENST00000625084.1(PLCL1):n.44+59192T>C 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 0.864 in 152,106 control chromosomes in the GnomAD database, including 57,024 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 0.86 (57024 hom., cov: 31)
• Consequence: PLCL1 ENST00000625084.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690

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=-0.98).
• 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	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL1	ENST00000625084.1	n.44+59192T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131366 AN: 151988 Hom.: 56981 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.864 AC: 131463 AN: 152106 Hom.: 57024 Cov.: 31 AF XY: 0.867 AC XY: 64437 AN XY: 74358

Gnomad4 AFR AF: 0.794

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.869

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.947

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.881

Gnomad4 OTH AF: 0.876

Alfa AF: 0.855 Hom.: 7931

Bravo AF: 0.862

Asia WGS AF: 0.956 AC: 3327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	1.4
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2342753; hg19: chr2-199073334;