rs4682314

Positions:

• chr3-111786766-C-A
• chr3-111786766-C-G

Variant summary

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

The ENST00000477665.2(PLCXD2):​c.*33+54063C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,816 control chromosomes in the GnomAD database, including 17,364 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 0.43 (17364 hom., cov: 31)
• Consequence: PLCXD2 ENST00000477665.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

Genes affected

PLCXD2 (HGNC:26462): (phosphatidylinositol specific phospholipase C X domain containing 2) Predicted to enable phosphoric diester hydrolase activity. Predicted to be involved in lipid catabolic process and signal transduction. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

LOC107984087 (HGNC:):

PHLDB2 (HGNC:29573): (pleckstrin homology like domain family B member 2) Enables cadherin binding activity. Involved in several processes, including negative regulation of focal adhesion assembly; regulation of cytoskeleton organization; and regulation of embryonic development. Located in several cellular components, including basal cortex; cell leading edge; and intermediate filament cytoskeleton. Colocalizes with focal adhesion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC107984087	XR_001740848.2	n.317+2125G>T		intron_variant, non_coding_transcript_variant
PHLDB2	NM_001134437.2	c.-49+54063C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLCXD2	ENST00000393934.7	c.867-59055C>A		intron_variant		1
PLCXD2	ENST00000477665.2	c.*33+54063C>A		intron_variant		1
PHLDB2	ENST00000393923.7	c.-49+54063C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65439 AN: 151698 Hom.: 17346 Cov.: 31

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.646

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.431 AC: 65458 AN: 151816 Hom.: 17364 Cov.: 31 AF XY: 0.440 AC XY: 32627 AN XY: 74166

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.774

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.530

Gnomad4 OTH AF: 0.480

Alfa AF: 0.526 Hom.: 43406

Bravo AF: 0.414

Asia WGS AF: 0.670 AC: 2332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.85

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: rs4682314; hg19: chr3-111505613;