chr2-198051010-C-T

Variant names:

• chr2-198051010-C-T
• rs2117339
• NM_006226.4:c.241-32748C>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.241-32748C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 152,064 control chromosomes in the GnomAD database, including 14,858 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 0.43 (14858 hom., cov: 33)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.287
• Publications: 16 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.241-32748C>T		intron_variant	Intron 1 of 5	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.19-32748C>T		intron_variant	Intron 1 of 5		XP_005246700.1
PLCL1	XM_017004339.3	c.4-32748C>T		intron_variant	Intron 1 of 5		XP_016859828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL1	ENST00000428675.6	c.241-32748C>T		intron_variant	Intron 1 of 5	1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.19-32748C>T		intron_variant	Intron 1 of 5	5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.*13-32748C>T		intron_variant	Intron 2 of 6	2		ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64897 AN: 151946 Hom.: 14865 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.404

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.515

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.427 AC: 64896 AN: 152064 Hom.: 14858 Cov.: 33 AF XY: 0.425 AC XY: 31567 AN XY: 74332

African (AFR) AF: 0.286 AC: 11865 AN: 41470

American (AMR) AF: 0.423 AC: 6466 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1787 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1145 AN: 5176

South Asian (SAS) AF: 0.572 AC: 2756 AN: 4818

European-Finnish (FIN) AF: 0.404 AC: 4264 AN: 10554

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.515 AC: 34992 AN: 67978

Other (OTH) AF: 0.464 AC: 981 AN: 2112

Alfa AF: 0.447 Hom.: 2027

Bravo AF: 0.414

Asia WGS AF: 0.385 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.74
PhyloP100		-0.29
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: rs2117339; hg19: chr2-198915734;