rs4550664

Variant names:

• chr2-197826681-A-G
• rs4550664
• NM_006226.4:c.240+21342A>G

Variant summary

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

The NM_006226.4(PLCL1):​c.240+21342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,120 control chromosomes in the GnomAD database, including 6,633 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 0.27 (6633 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 15 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]

ENSG00000286020 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.483 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.240+21342A>G		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.240+21342A>G		intron	N/A	ENSP00000402861.1	Q15111-1
	PLCL1	ENST00000487695.6	TSL:5	c.18+16359A>G		intron	N/A	ENSP00000457588.1	H3BUD4
	PLCL1	ENST00000435320.1	TSL:2	n.240+21342A>G		intron	N/A	ENSP00000410488.1	F8WAR2

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40555 AN: 152002 Hom.: 6629 Cov.: 32

Gnomad AFR AF: 0.0782

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.267 AC: 40565 AN: 152120 Hom.: 6633 Cov.: 32 AF XY: 0.270 AC XY: 20080 AN XY: 74354

African (AFR) AF: 0.0780 AC: 3240 AN: 41564

American (AMR) AF: 0.343 AC: 5235 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 931 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2567 AN: 5142

South Asian (SAS) AF: 0.343 AC: 1657 AN: 4824

European-Finnish (FIN) AF: 0.393 AC: 4156 AN: 10574

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.323 AC: 21938 AN: 67970

Other (OTH) AF: 0.254 AC: 535 AN: 2110

Alfa AF: 0.280 Hom.: 1604

Bravo AF: 0.256

Asia WGS AF: 0.403 AC: 1397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.12
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: rs4550664; hg19: chr2-198691405;