rs1016883

Variant names:

• chr2-198016944-G-A
• rs1016883
• NM_006226.4:c.241-66814G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-198016944-G-A
• chr2-198016944-G-C
• chr2-198016944-G-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.241-66814G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,056 control chromosomes in the GnomAD database, including 3,092 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 0.20 (3092 hom., cov: 32)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.318
• Publications: 41 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.241-66814G>A		intron_variant	Intron 1 of 5	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.19-66814G>A		intron_variant	Intron 1 of 5		XP_005246700.1
PLCL1	XM_017004339.3	c.3+14936G>A		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.241-66814G>A		intron_variant	Intron 1 of 5	1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.19-66814G>A		intron_variant	Intron 1 of 5	5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.*12+14936G>A		intron_variant	Intron 2 of 6	2		ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30218 AN: 151938 Hom.: 3079 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.199 AC: 30272 AN: 152056 Hom.: 3092 Cov.: 32 AF XY: 0.202 AC XY: 14987 AN XY: 74326

African (AFR) AF: 0.224 AC: 9276 AN: 41466

American (AMR) AF: 0.200 AC: 3050 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 844 AN: 3470

East Asian (EAS) AF: 0.264 AC: 1364 AN: 5170

South Asian (SAS) AF: 0.131 AC: 631 AN: 4816

European-Finnish (FIN) AF: 0.215 AC: 2265 AN: 10558

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.178 AC: 12071 AN: 67984

Other (OTH) AF: 0.214 AC: 451 AN: 2112

Alfa AF: 0.185 Hom.: 11460

Bravo AF: 0.205

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.71
DANN	Benign	0.70
PhyloP100		-0.32
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: rs1016883; hg19: chr2-198881668;