rs2803990

chr10-132746836-A-G

Variant summary

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

The NM_005539.5(INPP5A):c.733-2681A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,208 control chromosomes in the GnomAD database, including 5,203 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 0.26 (5203 hom., cov: 34)
• Consequence: INPP5A NM_005539.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.440

Genes affected

INPP5A (HGNC:6076): (inositol polyphosphate-5-phosphatase A) The protein encoded by this gene is a membrane-associated type I inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase. InsP3 5-phosphatases hydrolyze Ins(1,4,5)P3, which mobilizes intracellular calcium and acts as a second messenger mediating cell responses to various stimulation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP5A	NM_005539.5	c.733-2681A>G		intron_variant		ENST00000368594.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP5A	ENST00000368594.8	c.733-2681A>G		intron_variant		1	NM_005539.5	P1
INPP5A	ENST00000368593.7	c.733-2681A>G		intron_variant		1
INPP5A	ENST00000342652.6	c.647-18937A>G		intron_variant		5
INPP5A	ENST00000498337.1	n.195-2681A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39199 AN: 152090 Hom.: 5197 Cov.: 34

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.258

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

GnomAD4 genome AF: 0.258 AC: 39243 AN: 152208 Hom.: 5203 Cov.: 34 AF XY: 0.254 AC XY: 18933 AN XY: 74440

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.249

Gnomad4 EAS AF: 0.131

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.257

Alfa AF: 0.267 Hom.: 883

Bravo AF: 0.256

Asia WGS AF: 0.226 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	2.8
Dann	Benign	0.63

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: rs2803990; hg19: chr10-134560340;