rs11681576

Variant names:

• chr2-198113263-C-A
• rs11681576
• NM_006226.4:c.3105+9327C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006226.4(PLCL1):​c.3105+9327C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,810 control chromosomes in the GnomAD database, including 13,347 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 0.40 (13347 hom., cov: 33)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.3105+9327C>A		intron_variant	Intron 5 of 5	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.2883+9327C>A		intron_variant	Intron 5 of 5		XP_005246700.1
PLCL1	XM_005246644.5	c.2868+9327C>A		intron_variant	Intron 5 of 5		XP_005246701.1
PLCL1	XM_017004339.3	c.2868+9327C>A		intron_variant	Intron 5 of 5		XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.3105+9327C>A		intron_variant	Intron 5 of 5	1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.2883+9327C>A		intron_variant	Intron 5 of 5	5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.*2877+9327C>A		intron_variant	Intron 6 of 6	2		ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61178 AN: 151692 Hom.: 13349 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.403 AC: 61193 AN: 151810 Hom.: 13347 Cov.: 33 AF XY: 0.414 AC XY: 30681 AN XY: 74192

African (AFR) AF: 0.235 AC: 9745 AN: 41494

American (AMR) AF: 0.505 AC: 7686 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1424 AN: 3462

East Asian (EAS) AF: 0.550 AC: 2818 AN: 5124

South Asian (SAS) AF: 0.616 AC: 2970 AN: 4820

European-Finnish (FIN) AF: 0.523 AC: 5528 AN: 10562

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29738 AN: 67808

Other (OTH) AF: 0.414 AC: 873 AN: 2108

Alfa AF: 0.432 Hom.: 24051

Bravo AF: 0.393

Asia WGS AF: 0.580 AC: 2017 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.57
PhyloP100		0.087
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11681576; hg19: chr2-198977987;