10-119805503-C-G

Variant names:

• chr10-119805503-C-G
• rs2273749
• NM_014937.4:c.1319+42C>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001441000.1(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_001441000.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 5 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001441000.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	NM_014937.4	MANE Select	c.1319+42C>G		intron	N/A	NP_055752.1
	INPP5F	NM_001441000.1		c.1319+42C>G		intron	N/A	NP_001427929.1
	INPP5F	NM_001441001.1		c.1268+42C>G		intron	N/A	NP_001427930.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5F	ENST00000650623.2	MANE Select	c.1319+42C>G		intron	N/A	ENSP00000497527.1
	INPP5F	ENST00000964566.1		c.1319+42C>G		intron	N/A	ENSP00000634625.1
	INPP5F	ENST00000895117.1		c.1262+42C>G		intron	N/A	ENSP00000565176.1

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

GnomAD2 exomes AF: 0.297 AC: 72305 AN: 243670 AF XY: 0.289

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 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

African (AFR) AF: 0.134 AC: 3687 AN: 27580

American (AMR) AF: 0.403 AC: 17459 AN: 43280

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 5560 AN: 24298

East Asian (EAS) AF: 0.603 AC: 23117 AN: 38332

South Asian (SAS) AF: 0.189 AC: 15093 AN: 79690

European-Finnish (FIN) AF: 0.244 AC: 12812 AN: 52518

Middle Eastern (MID) AF: 0.269 AC: 1395 AN: 5186

European-Non Finnish (NFE) AF: 0.285 AC: 244203 AN: 856686

Other (OTH) AF: 0.274 AC: 13980 AN: 50942

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

African (AFR) AF: 0.138 AC: 5722 AN: 41460

American (AMR) AF: 0.364 AC: 5554 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 774 AN: 3470

East Asian (EAS) AF: 0.553 AC: 2852 AN: 5158

South Asian (SAS) AF: 0.196 AC: 945 AN: 4824

European-Finnish (FIN) AF: 0.242 AC: 2546 AN: 10538

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19223 AN: 67956

Other (OTH) AF: 0.282 AC: 594 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	7.6
DANN	Benign	0.73
PhyloP100		-0.23
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: rs2273749; hg19: chr10-121565015; COSMIC: COSV62820043;