10-119811995-T-C

Variant names:

• chr10-119811995-T-C
• rs3781503
• NM_014937.4:c.1886+40T>C

Variant summary

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

The NM_014937.4(INPP5F):​c.1886+40T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 1,516,746 control chromosomes in the GnomAD database, including 162,710 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 0.43 (14696 hom., cov: 32)
  • Exomes 𝑓: 0.46 (148014 hom.)
• Consequence: INPP5F NM_014937.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 16 publications found

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]

ENSG00000293336 (HGNC:):

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 (SAS) allele frequency at 95% confidence interval = 0.66 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP5F	NM_014937.4	c.1886+40T>C		intron_variant	Intron 15 of 19	ENST00000650623.2	NP_055752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP5F	ENST00000650623.2	c.1886+40T>C		intron_variant	Intron 15 of 19		NM_014937.4	ENSP00000497527.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65835 AN: 151844 Hom.: 14673 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.243

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.459

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.418

GnomAD2 exomes AF: 0.441 AC: 109559 AN: 248564 AF XY: 0.456

Gnomad AFR exome AF: 0.429

Gnomad AMR exome AF: 0.314

Gnomad ASJ exome AF: 0.450

Gnomad EAS exome AF: 0.242

Gnomad FIN exome AF: 0.462

Gnomad NFE exome AF: 0.445

Gnomad OTH exome AF: 0.439

GnomAD4 exome AF: 0.459 AC: 626304 AN: 1364784 Hom.: 148014 Cov.: 21 AF XY: 0.466 AC XY: 318875 AN XY: 684300

African (AFR) AF: 0.424 AC: 13314 AN: 31402

American (AMR) AF: 0.321 AC: 14210 AN: 44336

Ashkenazi Jewish (ASJ) AF: 0.447 AC: 11350 AN: 25410

East Asian (EAS) AF: 0.226 AC: 8848 AN: 39204

South Asian (SAS) AF: 0.672 AC: 56511 AN: 84150

European-Finnish (FIN) AF: 0.458 AC: 24390 AN: 53256

Middle Eastern (MID) AF: 0.467 AC: 2593 AN: 5554

European-Non Finnish (NFE) AF: 0.458 AC: 468776 AN: 1024356

Other (OTH) AF: 0.461 AC: 26312 AN: 57116

GnomAD4 genome AF: 0.434 AC: 65896 AN: 151962 Hom.: 14696 Cov.: 32 AF XY: 0.434 AC XY: 32270 AN XY: 74278

African (AFR) AF: 0.427 AC: 17710 AN: 41444

American (AMR) AF: 0.365 AC: 5579 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1560 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1260 AN: 5170

South Asian (SAS) AF: 0.679 AC: 3270 AN: 4816

European-Finnish (FIN) AF: 0.459 AC: 4835 AN: 10536

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.446 AC: 30330 AN: 67932

Other (OTH) AF: 0.417 AC: 879 AN: 2110

Alfa AF: 0.439 Hom.: 44300

Bravo AF: 0.420

Asia WGS AF: 0.465 AC: 1619 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	0.010
DANN	Benign	0.53
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3781503; hg19: chr10-121571507; COSMIC: COSV107452811; COSMIC: COSV107452811;