chr2-198115039-T-C

Variant names:

• chr2-198115039-T-C
• rs7603309
• NM_006226.4:c.3105+11103T>C

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+11103T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 151,724 control chromosomes in the GnomAD database, including 2,359 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 0.16 (2359 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 3 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.217 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+11103T>C		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+11103T>C		intron	N/A	ENSP00000402861.1	Q15111-1
	PLCL1	ENST00000487695.6	TSL:5	c.2883+11103T>C		intron	N/A	ENSP00000457588.1	H3BUD4
	PLCL1	ENST00000435320.1	TSL:2	n.*2877+11103T>C		intron	N/A	ENSP00000410488.1	F8WAR2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24366 AN: 151606 Hom.: 2362 Cov.: 31

Gnomad AFR AF: 0.0641

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0846

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.161 AC: 24364 AN: 151724 Hom.: 2359 Cov.: 31 AF XY: 0.156 AC XY: 11530 AN XY: 74140

African (AFR) AF: 0.0641 AC: 2657 AN: 41462

American (AMR) AF: 0.162 AC: 2467 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3468

East Asian (EAS) AF: 0.187 AC: 955 AN: 5110

South Asian (SAS) AF: 0.191 AC: 919 AN: 4808

European-Finnish (FIN) AF: 0.0846 AC: 896 AN: 10592

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14909 AN: 67792

Other (OTH) AF: 0.199 AC: 420 AN: 2106

Alfa AF: 0.183 Hom.: 1120

Bravo AF: 0.162

Asia WGS AF: 0.174 AC: 603 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		0.073
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: rs7603309; hg19: chr2-198979763;