rs1456554

chr2-198268390-T-C

Variant summary

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

The ENST00000625084.1(PLCL1):n.45-86905T>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 0.0914 in 152,192 control chromosomes in the GnomAD database, including 818 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 0.091 (818 hom., cov: 32)
• Consequence: PLCL1 ENST00000625084.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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.45-86905T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13885 AN: 152074 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0914 AC: 13904 AN: 152192 Hom.: 818 Cov.: 32 AF XY: 0.0899 AC XY: 6692 AN XY: 74410

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.100

Gnomad4 ASJ AF: 0.0816

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0270

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0678 Hom.: 826

Bravo AF: 0.0982

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.27
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1456554; hg19: chr2-199133114;