dbSNP rs9660548: INPP5B:c.*1750A>T (chr1-37860565-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005540.3(INPP5B):c.*1750A>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,322 control chromosomes in the GnomAD database, including 1,328 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 0.12 ( 1328 hom., cov: 33)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

INPP5B
NM_005540.3 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

2 publications found

Variant links:

COSMIC-nc: COSV65959959

Genes affected

INPP5B (HGNC:6077): (inositol polyphosphate-5-phosphatase B) This gene encodes a member of a family of inositol polyphosphate-5-phosphatases. These enzymes function in the regulation of calcium signaling by inactivating inositol phosphates. The encoded protein is localized to the cytosol and mitochondria, and associates with membranes through an isoprenyl modification near the C-terminus. Alternatively spliced transcript variants of this gene have been described. [provided by RefSeq, Jul 2014]

INPP5B links:

INPP5B-AS1 (HGNC:40304): (INPP5B antisense RNA 1)

INPP5B-AS1 links:

Genome browser will be placed here

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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP5B	NM_005540.3 link	c.*1750A>T		downstream_gene_variant		ENST00000373024.8	NP_005531.2	P32019-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
INPP5B	ENST00000373024.8 link	c.*1750A>T	downstream_gene_variant	1	NM_005540.3	ENSP00000362115.3	P32019-2
INPP5B-AS1	ENST00000419993.1 link	n.-132T>A	upstream_gene_variant	5
INPP5B	ENST00000373027.5 link	c.*1750A>T	downstream_gene_variant	2		ENSP00000362118.1	P32019-3

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18462

AN:

152168

Hom.:

1326

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0503

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.0596

Gnomad EAS

AF:

0.0816

Gnomad SAS

AF:

0.0990

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.118

GnomAD4 exome

AF:

0.139

AC:

AN:

Hom.:

AF XY:

0.115

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.115

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.595

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.121

AC:

18464

AN:

152286

Hom.:

1328

Cov.:

AF XY:

0.122

AC XY:

9102

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0502

AC:

2086

AN:

41572

American (AMR)

AF:

0.143

AC:

2189

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0596

AC:

207

AN:

3472

East Asian (EAS)

AF:

0.0814

AC:

422

AN:

5184

South Asian (SAS)

AF:

0.0995

AC:

480

AN:

4826

European-Finnish (FIN)

AF:

0.199

AC:

2103

AN:

10594

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.157

AC:

10696

AN:

68014

Other (OTH)

AF:

0.116

AC:

245

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

845

1689

2534

3378

4223

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.137

Hom.:

175

Bravo

AF:

0.113

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

6.9

(source)

DANN

Benign

0.66

PhyloP100

-0.058

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over