chr2-198055418-T-C

Position:

• chr2-198055418-T-C

Variant summary

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

The NM_006226.4(PLCL1):​c.241-28340T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 149,312 control chromosomes in the GnomAD database, including 40,034 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 0.72 (40034 hom., cov: 23)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-1.14).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.241-28340T>C		intron_variant		ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.19-28340T>C		intron_variant			XP_005246700.1
PLCL1	XM_017004339.3	c.4-28340T>C		intron_variant			XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.241-28340T>C		intron_variant		1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.19-28340T>C		intron_variant		5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.*13-28340T>C		intron_variant		2		ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 108082 AN: 149190 Hom.: 39993 Cov.: 23

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.754

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.678

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.685

Gnomad OTH AF: 0.745

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

GnomAD4 genome AF: 0.724 AC: 108176 AN: 149312 Hom.: 40034 Cov.: 23 AF XY: 0.723 AC XY: 52553 AN XY: 72722

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.754

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.685

Gnomad4 OTH AF: 0.743

Alfa AF: 0.701 Hom.: 17541

Bravo AF: 0.731

Asia WGS AF: 0.587 AC: 2042 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	9.7
DANN	Benign	0.57

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: rs2342558; hg19: chr2-198920142;