chr2-197825277-T-C

Position:

• chr2-197825277-T-C

Variant summary

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

The NM_006226.4(PLCL1):​c.240+19938T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,082 control chromosomes in the GnomAD database, including 41,174 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 (41174 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.892 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.240+19938T>C		intron_variant		ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.18+14955T>C		intron_variant			XP_005246700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.240+19938T>C		intron_variant		1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.18+14955T>C		intron_variant		5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.240+19938T>C		intron_variant		2		ENSP00000410488.1
ENSG00000286020	ENST00000650958.1	n.133-6616A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110374 AN: 151964 Hom.: 41130 Cov.: 32

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.726 AC: 110473 AN: 152082 Hom.: 41174 Cov.: 32 AF XY: 0.723 AC XY: 53739 AN XY: 74320

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.500

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.741

Alfa AF: 0.684 Hom.: 14997

Bravo AF: 0.737

Asia WGS AF: 0.594 AC: 2068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.022
DANN	Benign	0.57

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: rs700671; hg19: chr2-198690001;