rs6738825

Variant names:

• chr2-198032171-A-G
• rs6738825
• NM_006226.4:c.241-51587A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-198032171-A-G
• chr2-198032171-A-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.241-51587A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 152,032 control chromosomes in the GnomAD database, including 18,473 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 (18473 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64
• Publications: 61 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.528 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.241-51587A>G		intron_variant	Intron 1 of 5	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.19-51587A>G		intron_variant	Intron 1 of 5		XP_005246700.1
PLCL1	XM_017004339.3	c.3+30163A>G		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.241-51587A>G		intron_variant	Intron 1 of 5	1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.19-51587A>G		intron_variant	Intron 1 of 5	5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.*12+30163A>G		intron_variant	Intron 2 of 6	2		ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74125 AN: 151914 Hom.: 18474 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.546

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.488 AC: 74146 AN: 152032 Hom.: 18473 Cov.: 32 AF XY: 0.484 AC XY: 35965 AN XY: 74328

African (AFR) AF: 0.523 AC: 21696 AN: 41462

American (AMR) AF: 0.441 AC: 6739 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1768 AN: 3472

East Asian (EAS) AF: 0.223 AC: 1154 AN: 5182

South Asian (SAS) AF: 0.545 AC: 2629 AN: 4824

European-Finnish (FIN) AF: 0.395 AC: 4169 AN: 10552

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.505 AC: 34342 AN: 67952

Other (OTH) AF: 0.506 AC: 1067 AN: 2110

Alfa AF: 0.500 Hom.: 57025

Bravo AF: 0.487

Asia WGS AF: 0.387 AC: 1349 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.48
PhyloP100		1.6
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: rs6738825; hg19: chr2-198896895;