chr2-198170225-C-T

Variant names:

• chr2-198170225-C-T
• rs12476075
• ENST00000625084.1:n.44+20807C>T

Variant summary

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

The ENST00000625084.1(PLCL1):​n.44+20807C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 152,192 control chromosomes in the GnomAD database, including 63,353 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 0.91 (63353 hom., cov: 31)
• Consequence: PLCL1 ENST00000625084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.427
• Publications: 2 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=-0.98).
• 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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000625084.1	n.44+20807C>T		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138692 AN: 152074 Hom.: 63300 Cov.: 31

Gnomad AFR AF: 0.940

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.889

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.912 AC: 138802 AN: 152192 Hom.: 63353 Cov.: 31 AF XY: 0.913 AC XY: 67915 AN XY: 74400

African (AFR) AF: 0.940 AC: 39019 AN: 41516

American (AMR) AF: 0.916 AC: 14005 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3174 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5177 AN: 5184

South Asian (SAS) AF: 0.956 AC: 4613 AN: 4824

European-Finnish (FIN) AF: 0.881 AC: 9329 AN: 10590

Middle Eastern (MID) AF: 0.963 AC: 283 AN: 294

European-Non Finnish (NFE) AF: 0.889 AC: 60475 AN: 68010

Other (OTH) AF: 0.916 AC: 1932 AN: 2110

Alfa AF: 0.900 Hom.: 13974

Bravo AF: 0.916

Asia WGS AF: 0.975 AC: 3390 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	0.41
DANN	Benign	0.39
PhyloP100		-0.43

Splicing

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

Other links and lift over

dbSNP: rs12476075; hg19: chr2-199034949;