2-198520997-C-T

Variant names:

• chr2-198520997-C-T
• rs2054125
• ENST00000472193.1:n.346-50357C>T

Variant summary

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

The ENST00000472193.1(PLCL1):​n.346-50357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 152,264 control chromosomes in the GnomAD database, including 174 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 0.039 (174 hom., cov: 32)
• Consequence: PLCL1 ENST00000472193.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 4 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]

ENSG00000225421 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105373831	XR_923759.3	n.135-25784G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000472193.1	n.346-50357C>T		intron_variant	Intron 3 of 4	2
ENSG00000225421	ENST00000637390.1	n.151-25784G>A		intron_variant	Intron 2 of 3	5
ENSG00000225421	ENST00000829906.1	n.125-25784G>A		intron_variant	Intron 2 of 3
ENSG00000225421	ENST00000829907.1	n.318-25784G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5894 AN: 152146 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.00917

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0544

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0541

Gnomad OTH AF: 0.0459

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

GnomAD4 genome AF: 0.0387 AC: 5894 AN: 152264 Hom.: 174 Cov.: 32 AF XY: 0.0390 AC XY: 2900 AN XY: 74438

African (AFR) AF: 0.00914 AC: 380 AN: 41564

American (AMR) AF: 0.0543 AC: 831 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4822

European-Finnish (FIN) AF: 0.0742 AC: 786 AN: 10598

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0541 AC: 3678 AN: 68020

Other (OTH) AF: 0.0454 AC: 96 AN: 2114

Alfa AF: 0.0401 Hom.: 68

Bravo AF: 0.0367

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.66
PhyloP100		0.055

Splicing

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

Other links and lift over

dbSNP: rs2054125; hg19: chr2-199385721;