rs3771367

Variant names:

• chr2-198132315-G-A
• rs3771367
• NM_006226.4:c.3106-14465G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-198132315-G-A
• chr2-198132315-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.3106-14465G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 151,900 control chromosomes in the GnomAD database, including 10,911 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 0.37 (10911 hom., cov: 31)
• Consequence: PLCL1 NM_006226.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL1	NM_006226.4	c.3106-14465G>A		intron_variant	Intron 5 of 5	ENST00000428675.6	NP_006217.3
PLCL1	XM_005246643.5	c.2884-14465G>A		intron_variant	Intron 5 of 5		XP_005246700.1
PLCL1	XM_005246644.5	c.2869-14465G>A		intron_variant	Intron 5 of 5		XP_005246701.1
PLCL1	XM_017004339.3	c.2869-14465G>A		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.3106-14465G>A		intron_variant	Intron 5 of 5	1	NM_006226.4	ENSP00000402861.1
PLCL1	ENST00000487695.6	c.2884-14465G>A		intron_variant	Intron 5 of 5	5		ENSP00000457588.1
PLCL1	ENST00000435320.1	n.*2878-14465G>A		intron_variant	Intron 6 of 6	2		ENSP00000410488.1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56664 AN: 151782 Hom.: 10909 Cov.: 31

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.317

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.373 AC: 56683 AN: 151900 Hom.: 10911 Cov.: 31 AF XY: 0.368 AC XY: 27303 AN XY: 74186

African (AFR) AF: 0.305 AC: 12655 AN: 41428

American (AMR) AF: 0.346 AC: 5277 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1692 AN: 3472

East Asian (EAS) AF: 0.445 AC: 2292 AN: 5154

South Asian (SAS) AF: 0.318 AC: 1528 AN: 4808

European-Finnish (FIN) AF: 0.333 AC: 3506 AN: 10540

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28339 AN: 67942

Other (OTH) AF: 0.403 AC: 852 AN: 2112

Alfa AF: 0.371 Hom.: 1855

Bravo AF: 0.373

Asia WGS AF: 0.355 AC: 1232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.26
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: rs3771367; hg19: chr2-198997039;