rs16824514

Variant names:

• chr1-37930275-A-T
• rs16824514
• ENST00000373021:c.*1210T>A

Variant summary

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

The ENST00000373021(INPP5B):​c.*1210T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 152,044 control chromosomes in the GnomAD database, including 27,234 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 0.57 (27234 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: INPP5B ENST00000373021 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.71 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INPP5B	NM_005540.3	c.532+1638T>A		intron_variant	Intron 7 of 23	ENST00000373024.8	NP_005531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INPP5B	ENST00000373021	c.*1210T>A		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000362112.1
INPP5B	ENST00000373024.8	c.532+1638T>A		intron_variant	Intron 7 of 23	1	NM_005540.3	ENSP00000362115.3
INPP5B	ENST00000373026.5	c.772+1398T>A		intron_variant	Intron 6 of 22	5		ENSP00000362117.1
INPP5B	ENST00000373027.5	c.40+1398T>A		intron_variant	Intron 1 of 17	2		ENSP00000362118.1

Frequencies

GnomAD3 genomes AF: 0.568 AC: 86276 AN: 151924 Hom.: 27222 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.586

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.568 AC: 86310 AN: 152044 Hom.: 27234 Cov.: 33 AF XY: 0.568 AC XY: 42204 AN XY: 74316

Gnomad4 AFR AF: 0.272

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.744

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.581

Alfa AF: 0.630 Hom.: 4007

Bravo AF: 0.537

Asia WGS AF: 0.564 AC: 1961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.3
DANN	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs16824514; hg19: chr1-38395947;