2-198223806-A-G

Variant names:

• chr2-198223806-A-G
• rs7421388
• ENST00000625084.1:n.44+74388A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000625084.1(PLCL1):​n.44+74388A>G variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000625084.1	n.44+74388A>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.791 AC: 32806 AN: 41456

American (AMR) AF: 0.856 AC: 13084 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2790 AN: 3472

East Asian (EAS) AF: 0.998 AC: 5172 AN: 5184

South Asian (SAS) AF: 0.918 AC: 4420 AN: 4816

European-Finnish (FIN) AF: 0.791 AC: 8374 AN: 10586

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55276 AN: 67984

Other (OTH) AF: 0.832 AC: 1755 AN: 2110

Alfa AF: 0.839 Hom.: 83526

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
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs7421388; hg19: chr2-199088530;