chr2-197995704-T-C

Position:

• chr2-197995704-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.241-88054T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,972 control chromosomes in the GnomAD database, including 21,025 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 0.51 (21025 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL1	NM_006226.4	c.241-88054T>C		intron_variant		ENST00000428675.6
PLCL1	XM_005246643.5	c.19-88054T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL1	ENST00000428675.6	c.241-88054T>C		intron_variant		1	NM_006226.4	P1
PLCL1	ENST00000487695.6	c.19-88054T>C		intron_variant		5
PLCL1	ENST00000435320.1	c.241-6248T>C		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78081 AN: 151854 Hom.: 21015 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.493

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.599

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.514 AC: 78128 AN: 151972 Hom.: 21025 Cov.: 32 AF XY: 0.508 AC XY: 37736 AN XY: 74262

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.493

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.521

Alfa AF: 0.490 Hom.: 3811

Bravo AF: 0.521

Asia WGS AF: 0.390 AC: 1360 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.0
DANN	Benign	0.56

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: rs1866664; hg19: chr2-198860428;