rs2226462

chr3-38027267-C-T

Variant summary

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

The NM_006225.4(PLCD1):c.34+2239G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,060 control chromosomes in the GnomAD database, including 42,523 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 0.74 (42523 hom., cov: 32)
• Consequence: PLCD1 NM_006225.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.748

Genes affected

PLCD1 (HGNC:9060): (phospholipase C delta 1) This gene encodes a member of the phospholipase C family. Phospholipase C isozymes play critical roles in intracellular signal transduction by catalyzing the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) into the second messengers diacylglycerol (DAG) and inositol triphosphate (IP3). The encoded protein functions as a tumor suppressor in several types of cancer, and mutations in this gene are a cause of hereditary leukonychia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLCD1	NM_006225.4	c.34+2239G>A		intron_variant		ENST00000334661.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCD1	ENST00000334661.5	c.34+2239G>A		intron_variant		1	NM_006225.4	A1
PLCD1	ENST00000461445.5	n.54+2239G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112544 AN: 151942 Hom.: 42476 Cov.: 32

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.798

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.741 AC: 112649 AN: 152060 Hom.: 42523 Cov.: 32 AF XY: 0.741 AC XY: 55047 AN XY: 74314

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.621

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.699

Gnomad4 OTH AF: 0.734

Alfa AF: 0.719 Hom.: 18240

Bravo AF: 0.740

Asia WGS AF: 0.775 AC: 2697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.2
Dann	Benign	0.52

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: rs2226462; hg19: chr3-38068758;