2-198065082-C-T

Position:

• chr2-198065082-C-T

Variant summary

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

The NM_006226.4(PLCL1):​c.241-18676C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 151,996 control chromosomes in the GnomAD database, including 15,055 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 0.43 (15055 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.622

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.241-18676C>T		intron_variant		ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.19-18676C>T		intron_variant			XP_005246700.1
PLCL1	XM_017004339.3	c.4-18676C>T		intron_variant			XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.241-18676C>T		intron_variant		1	NM_006226.4	ENSP00000402861	P1
PLCL1	ENST00000487695.6	c.19-18676C>T		intron_variant		5		ENSP00000457588
PLCL1	ENST00000435320.1	c.*13-18676C>T		intron_variant, NMD_transcript_variant		2		ENSP00000410488

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65170 AN: 151878 Hom.: 15061 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.429 AC: 65170 AN: 151996 Hom.: 15055 Cov.: 32 AF XY: 0.426 AC XY: 31662 AN XY: 74302

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.522

Gnomad4 OTH AF: 0.468

Alfa AF: 0.509 Hom.: 9232

Bravo AF: 0.416

Asia WGS AF: 0.384 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.48

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: rs7572733; hg19: chr2-198929806;