rs2273749

chr10-119805503-C-Gchr10-119805503-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_014937.4(INPP5F):c.1319+42C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 1,330,484 control chromosomes in the GnomAD database, including 57,636 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 0.25 (5621 hom., cov: 32)
  • Exomes 𝑓: 0.29 (52015 hom.)
• Consequence: INPP5F NM_014937.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

Genes affected

INPP5F (HGNC:17054): (inositol polyphosphate-5-phosphatase F) The protein encoded by this gene is an inositol 1,4,5-trisphosphate (InsP3) 5-phosphatase and contains a Sac domain. The activity of this protein is specific for phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP5F	NM_014937.4	c.1319+42C>G		intron_variant		ENST00000650623.2
LOC105378513	XR_946359.3	n.465-806G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP5F	ENST00000650623.2	c.1319+42C>G		intron_variant			NM_014937.4	P1
	ENST00000636592.1	n.744+8985G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38602 AN: 151856 Hom.: 5617 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.278

GnomAD3 exomes AF: 0.297 AC: 72305 AN: 243670 Hom.: 11878 AF XY: 0.289 AC XY: 38086 AN XY: 131784

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.231

Gnomad EAS exome AF: 0.567

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.239

Gnomad NFE exome AF: 0.286

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.286 AC: 337306 AN: 1178512 Hom.: 52015 Cov.: 15 AF XY: 0.282 AC XY: 169358 AN XY: 600046

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.603

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.254 AC: 38619 AN: 151972 Hom.: 5621 Cov.: 32 AF XY: 0.256 AC XY: 19010 AN XY: 74256

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.283

Gnomad4 OTH AF: 0.282

Alfa AF: 0.194 Hom.: 634

Bravo AF: 0.259

Asia WGS AF: 0.363 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	7.6
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2273749; hg19: chr10-121565015; COSMIC: COSV62820043;