Genetic Variant NM_014937.4:c.1886+40T>C (chr10-119811995-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

16 publications found

Variant links:

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]

INPP5F links:

ENSG00000293336 (HGNC:):

ENSG00000293336 links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014937.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INPP5F	NM_014937.4	MANE Select	c.1886+40T>C	intron	N/A	NP_055752.1	Q9Y2H2-1
INPP5F	NM_001441000.1		c.1907+40T>C	intron	N/A	NP_001427929.1
INPP5F	NM_001441001.1		c.1835+40T>C	intron	N/A	NP_001427930.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
INPP5F	ENST00000650623.2	MANE Select	c.1886+40T>C	intron	N/A	ENSP00000497527.1	Q9Y2H2-1
INPP5F	ENST00000964566.1		c.1907+40T>C	intron	N/A	ENSP00000634625.1
INPP5F	ENST00000895117.1		c.1829+40T>C	intron	N/A	ENSP00000565176.1

Frequencies

GnomAD3 genomes

AF:

0.434

AC:

65835

AN:

151844

Hom.:

14673

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.466

AC XY:

318875

AN XY:

684300

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

16644

33288

49932

66576

83220

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13584

27168

40752

54336

67920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.434

AC:

65896

AN:

151962

Hom.:

14696

Cov.:

AF XY:

0.434

AC XY:

32270

AN XY:

74278

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1901

3801

5702

7602

9503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.010

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over