2-198208610-T-C

Variant names:

• chr2-198208610-T-C
• rs2342753
• ENST00000625084.1:n.44+59192T>C

Variant summary

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

The ENST00000625084.1(PLCL1):​n.44+59192T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.864 in 152,106 control chromosomes in the GnomAD database, including 57,024 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 0.86 (57024 hom., cov: 31)
• Consequence: PLCL1 ENST00000625084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690
• 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+59192T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.864 AC: 131366 AN: 151988 Hom.: 56981 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.869

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.864 AC: 131463 AN: 152106 Hom.: 57024 Cov.: 31 AF XY: 0.867 AC XY: 64437 AN XY: 74358

African (AFR) AF: 0.794 AC: 32917 AN: 41466

American (AMR) AF: 0.898 AC: 13703 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.869 AC: 3013 AN: 3468

East Asian (EAS) AF: 0.998 AC: 5161 AN: 5170

South Asian (SAS) AF: 0.947 AC: 4571 AN: 4828

European-Finnish (FIN) AF: 0.881 AC: 9345 AN: 10610

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59910 AN: 67992

Other (OTH) AF: 0.876 AC: 1852 AN: 2114

Alfa AF: 0.855 Hom.: 7931

Bravo AF: 0.862

Asia WGS AF: 0.956 AC: 3327 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	1.4
DANN	Benign	0.84
PhyloP100		-0.69

Splicing

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

Other links and lift over

dbSNP: rs2342753; hg19: chr2-199073334;