15-64857730-C-T

Variant names:

• chr15-64857730-C-T
• rs1107529
• NM_025201.5:c.280-2164C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025201.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHO2	NM_025201.5	MANE Select	c.280-2164C>T		intron	N/A	NP_079477.2
	PLEKHO2	NM_001195059.2		c.130-2164C>T		intron	N/A	NP_001181988.1	Q8TD55-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLEKHO2	ENST00000323544.5	TSL:1 MANE Select	c.280-2164C>T		intron	N/A	ENSP00000326706.4	Q8TD55-1
	PLEKHO2	ENST00000616065.4	TSL:1	c.130-2164C>T		intron	N/A	ENSP00000483505.1	Q8TD55-2
	ENSG00000249240	ENST00000437723.1	TSL:5	c.280-2164C>T		intron	N/A	ENSP00000397942.1	C9J4A7

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

African (AFR) AF: 0.145 AC: 6029 AN: 41498

American (AMR) AF: 0.247 AC: 3767 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3470

East Asian (EAS) AF: 0.753 AC: 3877 AN: 5152

South Asian (SAS) AF: 0.176 AC: 848 AN: 4818

European-Finnish (FIN) AF: 0.204 AC: 2160 AN: 10588

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10144 AN: 67996

Other (OTH) AF: 0.197 AC: 416 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.70
PhyloP100		-0.18
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: rs1107529; hg19: chr15-65149929;