rs13011342

Variant names:

• chr2-218622619-T-C
• rs13011342
• NM_032726.4:c.541-28T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032726.4(PLCD4):​c.541-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0365 in 1,501,908 control chromosomes in the GnomAD database, including 1,201 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 0.041 (168 hom., cov: 33)
  • Exomes 𝑓: 0.036 (1033 hom.)
• Consequence: PLCD4 NM_032726.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

Genes affected

PLCD4 (HGNC:9062): (phospholipase C delta 4) This gene encodes a member of the delta class of phospholipase C enzymes. Phospholipase C enzymes play a critical role in many cellular processes by hydrolyzing phosphatidylinositol 4,5-bisphosphate into two intracellular second messengers, inositol 1,4,5-trisphosphate and diacylglycerol. Expression of this gene may be a marker for cancer. [provided by RefSeq, Jan 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLCD4	NM_032726.4	c.541-28T>C		intron_variant	Intron 5 of 15	ENST00000450993.7	NP_116115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLCD4	ENST00000450993.7	c.541-28T>C		intron_variant	Intron 5 of 15	1	NM_032726.4	ENSP00000388631.2
PLCD4	ENST00000432688.5	c.541-28T>C		intron_variant	Intron 5 of 16	5		ENSP00000396185.1
PLCD4	ENST00000417849.5	c.541-28T>C		intron_variant	Intron 5 of 16	5		ENSP00000396942.1

Frequencies

GnomAD3 genomes AF: 0.0409 AC: 6226 AN: 152166 Hom.: 167 Cov.: 33

Gnomad AFR AF: 0.0543

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0228

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0336

Gnomad OTH AF: 0.0388

GnomAD3 exomes AF: 0.0396 AC: 7870 AN: 198798 Hom.: 192 AF XY: 0.0396 AC XY: 4315 AN XY: 109016

Gnomad AFR exome AF: 0.0525

Gnomad AMR exome AF: 0.0171

Gnomad ASJ exome AF: 0.0320

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.0431

Gnomad FIN exome AF: 0.0314

Gnomad NFE exome AF: 0.0333

Gnomad OTH exome AF: 0.0341

GnomAD4 exome AF: 0.0360 AC: 48531 AN: 1349624 Hom.: 1033 Cov.: 22 AF XY: 0.0362 AC XY: 24196 AN XY: 667736

Gnomad4 AFR exome AF: 0.0545

Gnomad4 AMR exome AF: 0.0186

Gnomad4 ASJ exome AF: 0.0328

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.0423

Gnomad4 FIN exome AF: 0.0312

Gnomad4 NFE exome AF: 0.0330

Gnomad4 OTH exome AF: 0.0385

GnomAD4 genome AF: 0.0409 AC: 6230 AN: 152284 Hom.: 168 Cov.: 33 AF XY: 0.0401 AC XY: 2984 AN XY: 74476

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.0336

Gnomad4 OTH AF: 0.0384

Alfa AF: 0.0351 Hom.: 18

Bravo AF: 0.0417

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.7
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs13011342; hg19: chr2-219487342;