rs4850447

Variant names:

• chr2-198209166-C-T
• rs4850447
• ENST00000625084.1:n.44+59748C>T

Variant summary

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

The ENST00000625084.1(PLCL1):​n.44+59748C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,140 control chromosomes in the GnomAD database, including 50,081 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 (50081 hom., cov: 33)
• Consequence: PLCL1 ENST00000625084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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=-1.02).
• 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+59748C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121747 AN: 152022 Hom.: 50075 Cov.: 33

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.945

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.826

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

GnomAD4 genome AF: 0.800 AC: 121787 AN: 152140 Hom.: 50081 Cov.: 33 AF XY: 0.805 AC XY: 59867 AN XY: 74378

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.828

Alfa AF: 0.822 Hom.: 6498

Bravo AF: 0.789

Asia WGS AF: 0.940 AC: 3268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.50

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4850447; hg19: chr2-199073890;