9-68740301-C-T

Variant names:

• chr9-68740301-C-T
• rs963707
• NM_003558.4:c.-242-2200C>T

Variant summary

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

The NM_003558.4(PIP5K1B):​c.-242-2200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.733 in 152,198 control chromosomes in the GnomAD database, including 41,967 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 0.73 (41967 hom., cov: 32)
• Consequence: PIP5K1B NM_003558.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIP5K1B	NM_003558.4	c.-242-2200C>T		intron_variant	Intron 1 of 15	ENST00000265382.8	NP_003549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIP5K1B	ENST00000265382.8	c.-242-2200C>T		intron_variant	Intron 1 of 15	1	NM_003558.4	ENSP00000265382.2
PIP5K1B	ENST00000541509.5	c.-86+34539C>T		intron_variant	Intron 1 of 13	2		ENSP00000438082.1
PIP5K1B	ENST00000377284.5	c.-243+409C>T		intron_variant	Intron 1 of 5	3		ENSP00000366498.1
PIP5K1B	ENST00000472907.6	n.497-2200C>T		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111470 AN: 152080 Hom.: 41918 Cov.: 32

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.759

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.719

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

GnomAD4 genome AF: 0.733 AC: 111577 AN: 152198 Hom.: 41967 Cov.: 32 AF XY: 0.730 AC XY: 54321 AN XY: 74396

African (AFR) AF: 0.912 AC: 37910 AN: 41552

American (AMR) AF: 0.680 AC: 10396 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2027 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3925 AN: 5178

South Asian (SAS) AF: 0.693 AC: 3345 AN: 4830

European-Finnish (FIN) AF: 0.647 AC: 6849 AN: 10586

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.658 AC: 44717 AN: 67974

Other (OTH) AF: 0.722 AC: 1525 AN: 2112

Alfa AF: 0.673 Hom.: 15734

Bravo AF: 0.740

Asia WGS AF: 0.766 AC: 2664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.39
PhyloP100		0.36
PromoterAI		0.015	Neutral
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: rs963707; hg19: chr9-71355217;