rs1456554

Variant names:

• chr2-198268390-T-C
• rs1456554
• ENST00000625084.1:n.45-86905T>C

Variant summary

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

The ENST00000625084.1(PLCL1):​n.45-86905T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,192 control chromosomes in the GnomAD database, including 818 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 0.091 (818 hom., cov: 32)
• Consequence: PLCL1 ENST00000625084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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.45-86905T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13885 AN: 152074 Hom.: 815 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0276

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0833

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

GnomAD4 genome AF: 0.0914 AC: 13904 AN: 152192 Hom.: 818 Cov.: 32 AF XY: 0.0899 AC XY: 6692 AN XY: 74410

African (AFR) AF: 0.163 AC: 6779 AN: 41518

American (AMR) AF: 0.100 AC: 1536 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 283 AN: 3470

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5178

South Asian (SAS) AF: 0.0270 AC: 130 AN: 4818

European-Finnish (FIN) AF: 0.0647 AC: 686 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0621 AC: 4220 AN: 68000

Other (OTH) AF: 0.0825 AC: 174 AN: 2110

Alfa AF: 0.0737 Hom.: 1549

Bravo AF: 0.0982

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.82
PhyloP100		-0.026

Splicing

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

Other links and lift over

dbSNP: rs1456554; hg19: chr2-199133114;