rs3771365

Positions:

• chr2-198112561-A-G

Variant summary

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

The NM_006226.4(PLCL1):​c.3105+8625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 151,712 control chromosomes in the GnomAD database, including 7,988 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 0.29 (7988 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.3105+8625A>G		intron_variant		ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.2883+8625A>G		intron_variant			XP_005246700.1
PLCL1	XM_005246644.5	c.2868+8625A>G		intron_variant			XP_005246701.1
PLCL1	XM_017004339.3	c.2868+8625A>G		intron_variant			XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.3105+8625A>G		intron_variant		1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.2883+8625A>G		intron_variant		5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.*2877+8625A>G		intron_variant		2		ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44009 AN: 151594 Hom.: 7988 Cov.: 32

Gnomad AFR AF: 0.0915

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.290 AC: 44010 AN: 151712 Hom.: 7988 Cov.: 32 AF XY: 0.303 AC XY: 22458 AN XY: 74106

Gnomad4 AFR AF: 0.0913

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.287

Alfa AF: 0.316 Hom.: 1056

Bravo AF: 0.276

Asia WGS AF: 0.492 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.76

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: rs3771365; hg19: chr2-198977285;