rs9660548

Variant names:

• chr1-37860565-T-A
• rs9660548
• NM_005540.3:c.*1750A>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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]

ENSG00000230955 (HGNC:40304): (INPP5B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -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	c.*1750A>T		downstream_gene_variant		ENST00000373024.8	NP_005531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP5B	ENST00000373024.8	c.*1750A>T		downstream_gene_variant		1	NM_005540.3	ENSP00000362115.3
INPP5B	ENST00000373027.5	c.*1750A>T		downstream_gene_variant		2		ENSP00000362118.1
ENSG00000230955	ENST00000419993.1	n.-132T>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18462 AN: 152168 Hom.: 1326 Cov.: 33

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: 5 AN: 36 Hom.: 0 AF XY: 0.115 AC XY: 3 AN XY: 26

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.121 AC: 18464 AN: 152286 Hom.: 1328 Cov.: 33 AF XY: 0.122 AC XY: 9102 AN XY: 74450

Gnomad4 AFR AF: 0.0502

Gnomad4 AMR AF: 0.143

Gnomad4 ASJ AF: 0.0596

Gnomad4 EAS AF: 0.0814

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.116

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
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9660548; hg19: chr1-38326237; COSMIC: COSV65959959;