rs9660548

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005540.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5B	NM_005540.3	MANE Select	c.*1750A>T		downstream_gene	N/A	NP_005531.2	P32019-2
	INPP5B	NM_001365820.1		c.*1750A>T		downstream_gene	N/A	NP_001352749.1	P32019-2
	INPP5B	NM_001365821.1		c.*1750A>T		downstream_gene	N/A	NP_001352750.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPP5B	ENST00000373024.8	TSL:1 MANE Select	c.*1750A>T		downstream_gene	N/A	ENSP00000362115.3	P32019-2
	INPP5B	ENST00000948250.1		c.*1750A>T		downstream_gene	N/A	ENSP00000618309.1
	INPP5B	ENST00000923582.1		c.*1750A>T		downstream_gene	N/A	ENSP00000593641.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.115 AC: 3 AN: 26

Other (OTH) AF: 0.250 AC: 1 AN: 4

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

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: 19 AN: 294

European-Non Finnish (NFE) AF: 0.157 AC: 10696 AN: 68014

Other (OTH) AF: 0.116 AC: 245 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.66
PhyloP100		-0.058

Splicing

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

Other links and lift over

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