rs1808850

chr2-198113937-A-Gchr2-198113937-A-T

Variant summary

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

The NM_006226.4(PLCL1):c.3105+10001A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 151,720 control chromosomes in the GnomAD database, including 58,182 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 0.87 (58182 hom., cov: 30)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0840

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCL1	NM_006226.4	c.3105+10001A>G		intron_variant		ENST00000428675.6
PLCL1	XM_005246643.5	c.2883+10001A>G		intron_variant
PLCL1	XM_005246644.5	c.2868+10001A>G		intron_variant
PLCL1	XM_017004339.3	c.2868+10001A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCL1	ENST00000428675.6	c.3105+10001A>G		intron_variant		1	NM_006226.4	P1
PLCL1	ENST00000487695.6	c.2883+10001A>G		intron_variant		5
PLCL1	ENST00000435320.1	c.*2877+10001A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.875 AC: 132679 AN: 151602 Hom.: 58166 Cov.: 30

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.872

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.957

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.883

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

GnomAD4 genome AF: 0.875 AC: 132744 AN: 151720 Hom.: 58182 Cov.: 30 AF XY: 0.876 AC XY: 64954 AN XY: 74118

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.888

Gnomad4 OTH AF: 0.884

Alfa AF: 0.892 Hom.: 55959

Bravo AF: 0.874

Asia WGS AF: 0.962 AC: 3335 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	12
Dann	Benign	0.75

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: rs1808850; hg19: chr2-198978661;