chr2-198104859-C-T

Variant names:

• chr2-198104859-C-T
• rs1304358
• NM_006226.4:c.3105+923C>T

Variant summary

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

The NM_006226.4(PLCL1):​c.3105+923C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,824 control chromosomes in the GnomAD database, including 20,019 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 0.49 (20019 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.3105+923C>T		intron_variant	Intron 5 of 5	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.2883+923C>T		intron_variant	Intron 5 of 5		XP_005246700.1
PLCL1	XM_005246644.5	c.2868+923C>T		intron_variant	Intron 5 of 5		XP_005246701.1
PLCL1	XM_017004339.3	c.2868+923C>T		intron_variant	Intron 5 of 5		XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.3105+923C>T		intron_variant	Intron 5 of 5	1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.2883+923C>T		intron_variant	Intron 5 of 5	5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.*2877+923C>T		intron_variant	Intron 6 of 6	2		ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74621 AN: 151704 Hom.: 20020 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.492 AC: 74631 AN: 151824 Hom.: 20019 Cov.: 32 AF XY: 0.504 AC XY: 37360 AN XY: 74172

African (AFR) AF: 0.279 AC: 11560 AN: 41420

American (AMR) AF: 0.581 AC: 8844 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.559 AC: 1940 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4117 AN: 5136

South Asian (SAS) AF: 0.595 AC: 2870 AN: 4822

European-Finnish (FIN) AF: 0.713 AC: 7524 AN: 10560

Middle Eastern (MID) AF: 0.476 AC: 138 AN: 290

European-Non Finnish (NFE) AF: 0.531 AC: 36054 AN: 67890

Other (OTH) AF: 0.473 AC: 998 AN: 2110

Alfa AF: 0.514 Hom.: 63906

Bravo AF: 0.474

Asia WGS AF: 0.664 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		0.30
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: rs1304358; hg19: chr2-198969583;