2-198131488-A-C

Position:

• chr2-198131488-A-C

Variant summary

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

The NM_006226.4(PLCL1):​c.3106-15292A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,060 control chromosomes in the GnomAD database, including 10,851 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 (10851 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL1	NM_006226.4	c.3106-15292A>C		intron_variant		ENST00000428675.6
PLCL1	XM_005246643.5	c.2884-15292A>C		intron_variant
PLCL1	XM_005246644.5	c.2869-15292A>C		intron_variant
PLCL1	XM_017004339.3	c.2869-15292A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL1	ENST00000428675.6	c.3106-15292A>C		intron_variant		1	NM_006226.4	P1
PLCL1	ENST00000487695.6	c.2884-15292A>C		intron_variant		5
PLCL1	ENST00000435320.1	c.*2878-15292A>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56357 AN: 151942 Hom.: 10851 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.371 AC: 56372 AN: 152060 Hom.: 10851 Cov.: 32 AF XY: 0.366 AC XY: 27168 AN XY: 74304

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.318

Gnomad4 FIN AF: 0.331

Gnomad4 NFE AF: 0.417

Gnomad4 OTH AF: 0.398

Alfa AF: 0.413 Hom.: 12987

Bravo AF: 0.372

Asia WGS AF: 0.351 AC: 1219 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	0.47
DANN	Benign	0.39

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: rs11884188; hg19: chr2-198996212;