rs770657

chr2-197809460-C-Achr2-197809460-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006226.4(PLCL1):c.240+4121C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,032 control chromosomes in the GnomAD database, including 41,411 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 0.73 (41411 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL1	NM_006226.4	c.240+4121C>A		intron_variant		ENST00000428675.6
PLCL1	XM_005246643.5	c.-845C>A		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL1	ENST00000428675.6	c.240+4121C>A		intron_variant		1	NM_006226.4	P1
PLCL1	ENST00000435320.1	c.240+4121C>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110630 AN: 151914 Hom.: 41362 Cov.: 31

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.500

Gnomad SAS AF: 0.657

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.743

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

GnomAD4 genome AF: 0.728 AC: 110734 AN: 152032 Hom.: 41411 Cov.: 31 AF XY: 0.725 AC XY: 53875 AN XY: 74288

Gnomad4 AFR AF: 0.905

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.607

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.743

Alfa AF: 0.699 Hom.: 17840

Bravo AF: 0.739

Asia WGS AF: 0.596 AC: 2076 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.6
Dann	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs770657; hg19: chr2-198674184;