2-198223806-A-G

Position:

• chr2-198223806-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+74388A>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 0.819 in 152,094 control chromosomes in the GnomAD database, including 51,178 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 0.82 (51178 hom., cov: 31)
• Consequence: PLCL1 ENST00000625084.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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 = 0.975 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+74388A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.819 AC: 124449 AN: 151978 Hom.: 51126 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.917

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.819 AC: 124555 AN: 152094 Hom.: 51178 Cov.: 31 AF XY: 0.821 AC XY: 61013 AN XY: 74354

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.918

Gnomad4 FIN AF: 0.791

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.832

Alfa AF: 0.840 Hom.: 65695

Bravo AF: 0.837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.2
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7421388; hg19: chr2-199088530;