15-64857730-C-T

Position:

• chr15-64857730-C-T

Variant summary

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

The NM_025201.5(PLEKHO2):​c.280-2164C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,116 control chromosomes in the GnomAD database, including 3,575 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 0.18 (3575 hom., cov: 32)
• Consequence: PLEKHO2 NM_025201.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184

Genes affected

PLEKHO2 (HGNC:30026): (pleckstrin homology domain containing O2) Predicted to act upstream of or within macrophage apoptotic process. Predicted to be located in extracellular region and ficolin-1-rich granule lumen. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000249240 (HGNC:):

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 = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLEKHO2	NM_025201.5	c.280-2164C>T		intron_variant		ENST00000323544.5	NP_079477.2
PLEKHO2	NM_001195059.2	c.130-2164C>T		intron_variant			NP_001181988.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLEKHO2	ENST00000323544.5	c.280-2164C>T		intron_variant		1	NM_025201.5	ENSP00000326706.4
PLEKHO2	ENST00000616065.4	c.130-2164C>T		intron_variant		1		ENSP00000483505.1
ENSG00000249240	ENST00000437723.1	c.280-2164C>T		intron_variant		5		ENSP00000397942.1
ENSG00000249240	ENST00000502574.1	n.414-2164C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27945 AN: 151998 Hom.: 3569 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.753

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.184 AC: 27970 AN: 152116 Hom.: 3575 Cov.: 32 AF XY: 0.190 AC XY: 14095 AN XY: 74358

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.753

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.197

Alfa AF: 0.165 Hom.: 313

Bravo AF: 0.192

Asia WGS AF: 0.423 AC: 1466 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	6.1
DANN	Benign	0.70

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: rs1107529; hg19: chr15-65149929;