chr3-17005540-A-T

Variant names:

• chr3-17005540-A-T
• rs4452313
• NM_001144382.2:c.328-4134A>T

Variant summary

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

The NM_001144382.2(PLCL2):​c.328-4134A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,074 control chromosomes in the GnomAD database, including 13,229 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 0.40 (13229 hom., cov: 32)
• Consequence: PLCL2 NM_001144382.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.371
• Publications: 29 publications found

Genes affected

PLCL2 (HGNC:9064): (phospholipase C like 2) Enables GABA receptor binding 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 B cell activation; gamma-aminobutyric acid signaling pathway; and negative regulation of B cell receptor signaling pathway. Predicted to be located in cytoplasm. [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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCL2	NM_001144382.2	c.328-4134A>T		intron_variant	Intron 1 of 5	ENST00000615277.5	NP_001137854.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCL2	ENST00000615277.5	c.328-4134A>T		intron_variant	Intron 1 of 5	1	NM_001144382.2	ENSP00000478458.1
PLCL2	ENST00000432376.5	c.-51-4134A>T		intron_variant	Intron 1 of 5	1		ENSP00000412836.1
PLCL2	ENST00000460467.1	n.439-4134A>T		intron_variant	Intron 1 of 2	1

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60560 AN: 151956 Hom.: 13200 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.399 AC: 60651 AN: 152074 Hom.: 13229 Cov.: 32 AF XY: 0.400 AC XY: 29742 AN XY: 74348

African (AFR) AF: 0.577 AC: 23935 AN: 41450

American (AMR) AF: 0.324 AC: 4958 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1085 AN: 3470

East Asian (EAS) AF: 0.545 AC: 2818 AN: 5174

South Asian (SAS) AF: 0.508 AC: 2452 AN: 4826

European-Finnish (FIN) AF: 0.316 AC: 3341 AN: 10570

Middle Eastern (MID) AF: 0.390 AC: 114 AN: 292

European-Non Finnish (NFE) AF: 0.303 AC: 20563 AN: 67974

Other (OTH) AF: 0.395 AC: 835 AN: 2116

Alfa AF: 0.203 Hom.: 429

Bravo AF: 0.407

Asia WGS AF: 0.537 AC: 1866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.21
DANN	Benign	0.72
PhyloP100		-0.37
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: rs4452313; hg19: chr3-17047032;