rs4038716

Variant names:

• chr2-198165965-T-C
• rs4038716
• ENST00000625084.1:n.44+16547T>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+16547T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,916 control chromosomes in the GnomAD database, including 11,686 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 0.38 (11686 hom., cov: 31)
• Consequence: PLCL1 ENST00000625084.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 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+16547T>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57349 AN: 151798 Hom.: 11692 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.378 AC: 57349 AN: 151916 Hom.: 11686 Cov.: 31 AF XY: 0.375 AC XY: 27823 AN XY: 74252

African (AFR) AF: 0.224 AC: 9290 AN: 41420

American (AMR) AF: 0.358 AC: 5455 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3468

East Asian (EAS) AF: 0.452 AC: 2331 AN: 5154

South Asian (SAS) AF: 0.357 AC: 1716 AN: 4812

European-Finnish (FIN) AF: 0.396 AC: 4181 AN: 10558

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30822 AN: 67948

Other (OTH) AF: 0.424 AC: 891 AN: 2102

Alfa AF: 0.397 Hom.: 2003

Bravo AF: 0.372

Asia WGS AF: 0.373 AC: 1297 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.73
PhyloP100		0.56

Splicing

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

Other links and lift over

dbSNP: rs4038716; hg19: chr2-199030689;