chr2-198131488-A-C

Variant names:

• chr2-198131488-A-C
• rs11884188
• NM_006226.4:c.3106-15292A>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.3106-15292A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 152,060 control chromosomes in the GnomAD database, including 10,851 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 0.37 (10851 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.418
• 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=-0.91).
• 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.3106-15292A>C		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.3106-15292A>C		intron	N/A	ENSP00000402861.1
	PLCL1	ENST00000487695.6	TSL:5	c.2884-15292A>C		intron	N/A	ENSP00000457588.1
	PLCL1	ENST00000435320.1	TSL:2	n.*2878-15292A>C		intron	N/A	ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56357 AN: 151942 Hom.: 10851 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.371 AC: 56372 AN: 152060 Hom.: 10851 Cov.: 32 AF XY: 0.366 AC XY: 27168 AN XY: 74304

African (AFR) AF: 0.294 AC: 12221 AN: 41498

American (AMR) AF: 0.346 AC: 5288 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1690 AN: 3466

East Asian (EAS) AF: 0.447 AC: 2309 AN: 5164

South Asian (SAS) AF: 0.318 AC: 1529 AN: 4812

European-Finnish (FIN) AF: 0.331 AC: 3499 AN: 10580

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28345 AN: 67944

Other (OTH) AF: 0.398 AC: 841 AN: 2112

Alfa AF: 0.406 Hom.: 16487

Bravo AF: 0.372

Asia WGS AF: 0.351 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.39
PhyloP100		-0.42
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: rs11884188; hg19: chr2-198996212;