chr2-198116378-C-T

Variant names:

• chr2-198116378-C-T
• rs17792650
• NM_006226.4:c.3105+12442C>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+12442C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,574 control chromosomes in the GnomAD database, including 9,233 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 0.33 (9233 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	NM_006226.4	MANE Select	c.3105+12442C>T		intron	N/A	NP_006217.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLCL1	ENST00000428675.6	TSL:1 MANE Select	c.3105+12442C>T		intron	N/A	ENSP00000402861.1
	PLCL1	ENST00000487695.6	TSL:5	c.2883+12442C>T		intron	N/A	ENSP00000457588.1
	PLCL1	ENST00000435320.1	TSL:2	n.*2877+12442C>T		intron	N/A	ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50373 AN: 151456 Hom.: 9236 Cov.: 31

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.370

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

GnomAD4 genome AF: 0.332 AC: 50377 AN: 151574 Hom.: 9233 Cov.: 31 AF XY: 0.328 AC XY: 24310 AN XY: 74020

African (AFR) AF: 0.181 AC: 7516 AN: 41422

American (AMR) AF: 0.333 AC: 5054 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1681 AN: 3462

East Asian (EAS) AF: 0.447 AC: 2285 AN: 5110

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4822

European-Finnish (FIN) AF: 0.329 AC: 3458 AN: 10518

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.407 AC: 27597 AN: 67776

Other (OTH) AF: 0.371 AC: 779 AN: 2098

Alfa AF: 0.345 Hom.: 1204

Bravo AF: 0.330

Asia WGS AF: 0.329 AC: 1136 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.8
DANN	Benign	0.37
PhyloP100		-0.16
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: rs17792650; hg19: chr2-198981102;