NM_003558.4:c.-86+30427C>G

Variant names:

• chr9-68773084-C-G
• rs17482181
• NM_003558.4:c.-86+30427C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003558.4(PIP5K1B):​c.-86+30427C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,138 control chromosomes in the GnomAD database, including 6,217 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 0.28 (6217 hom., cov: 32)
• Consequence: PIP5K1B NM_003558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 3 publications found

Genes affected

PIP5K1B (HGNC:8995): (phosphatidylinositol-4-phosphate 5-kinase type 1 beta) Predicted to enable 1-phosphatidylinositol-4-phosphate 5-kinase activity. Predicted to be involved in regulation of phosphatidylinositol 3-kinase signaling. Predicted to act upstream of or within phosphatidylinositol biosynthetic process. Located in uropod. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP5K1B	NM_003558.4	c.-86+30427C>G		intron_variant	Intron 2 of 15	ENST00000265382.8	NP_003549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP5K1B	ENST00000265382.8	c.-86+30427C>G		intron_variant	Intron 2 of 15	1	NM_003558.4	ENSP00000265382.2
PIP5K1B	ENST00000478500.3	n.-86+30427C>G		intron_variant	Intron 2 of 20	1		ENSP00000435778.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42438 AN: 152020 Hom.: 6213 Cov.: 32

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.315

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.279 AC: 42462 AN: 152138 Hom.: 6217 Cov.: 32 AF XY: 0.280 AC XY: 20842 AN XY: 74376

African (AFR) AF: 0.194 AC: 8061 AN: 41516

American (AMR) AF: 0.332 AC: 5071 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1054 AN: 3470

East Asian (EAS) AF: 0.187 AC: 968 AN: 5180

South Asian (SAS) AF: 0.311 AC: 1500 AN: 4824

European-Finnish (FIN) AF: 0.325 AC: 3436 AN: 10586

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.315 AC: 21426 AN: 67968

Other (OTH) AF: 0.282 AC: 596 AN: 2114

Alfa AF: 0.296 Hom.: 844

Bravo AF: 0.277

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.65
PhyloP100		-0.19
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: rs17482181; hg19: chr9-71388000; COSMIC: COSV55243983;