2-198113097-C-T

Variant names:

• chr2-198113097-C-T
• rs892515
• NM_006226.4:c.3105+9161C>T

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+9161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 151,604 control chromosomes in the GnomAD database, including 8,392 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 0.31 (8392 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006226.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	NM_006226.4	MANE Select	c.3105+9161C>T		intron	N/A	NP_006217.3	Q15111-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	ENST00000428675.6	TSL:1 MANE Select	c.3105+9161C>T		intron	N/A	ENSP00000402861.1	Q15111-1
	PLCL1	ENST00000487695.6	TSL:5	c.2883+9161C>T		intron	N/A	ENSP00000457588.1	H3BUD4
	PLCL1	ENST00000435320.1	TSL:2	n.*2877+9161C>T		intron	N/A	ENSP00000410488.1	F8WAR2

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47605 AN: 151488 Hom.: 8392 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.208

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.314 AC: 47613 AN: 151604 Hom.: 8392 Cov.: 32 AF XY: 0.326 AC XY: 24172 AN XY: 74048

African (AFR) AF: 0.184 AC: 7616 AN: 41402

American (AMR) AF: 0.409 AC: 6215 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1173 AN: 3466

East Asian (EAS) AF: 0.546 AC: 2787 AN: 5104

South Asian (SAS) AF: 0.471 AC: 2266 AN: 4812

European-Finnish (FIN) AF: 0.455 AC: 4805 AN: 10554

Middle Eastern (MID) AF: 0.207 AC: 60 AN: 290

European-Non Finnish (NFE) AF: 0.322 AC: 21801 AN: 67762

Other (OTH) AF: 0.307 AC: 645 AN: 2102

Alfa AF: 0.314 Hom.: 13783

Bravo AF: 0.305

Asia WGS AF: 0.487 AC: 1691 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.66
PhyloP100		0.36
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: rs892515; hg19: chr2-198977821;