rs3771367

chr2-198132315-G-Achr2-198132315-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006226.4(PLCL1):c.3106-14465G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,900 control chromosomes in the GnomAD database, including 10,911 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 0.37 (10911 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL1	NM_006226.4	c.3106-14465G>A		intron_variant		ENST00000428675.6
PLCL1	XM_005246643.5	c.2884-14465G>A		intron_variant
PLCL1	XM_005246644.5	c.2869-14465G>A		intron_variant
PLCL1	XM_017004339.3	c.2869-14465G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL1	ENST00000428675.6	c.3106-14465G>A		intron_variant		1	NM_006226.4	P1
PLCL1	ENST00000487695.6	c.2884-14465G>A		intron_variant		5
PLCL1	ENST00000435320.1	c.*2878-14465G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56664 AN: 151782 Hom.: 10909 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.373 AC: 56683 AN: 151900 Hom.: 10911 Cov.: 31 AF XY: 0.368 AC XY: 27303 AN XY: 74186

Gnomad4 AFR AF: 0.305

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.403

Alfa AF: 0.373 Hom.: 1819

Bravo AF: 0.373

Asia WGS AF: 0.355 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.3
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3771367; hg19: chr2-198997039;