2-98554381-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001134225.2(INPP4A):c.1458T>C(p.Thr486=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000833 in 1,613,742 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 33)
  • Exomes 𝑓: 0.00080 (19 hom.)
• Consequence: INPP4A NM_001134225.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.32

Genes affected

INPP4A (HGNC:6074): (inositol polyphosphate-4-phosphatase type I A) This gene encodes an Mg++ independent enzyme that hydrolyzes the 4-position phosphate from the inositol ring of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Multiple transcript variants encoding distinct isoforms have been described. [provided by RefSeq, Aug 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-98554381-T-C is Benign according to our data. Variant chr2-98554381-T-C is described in ClinVar as [Benign]. Clinvar id is 719006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.32 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00111 (169/152266) while in subpopulation EAS AF= 0.0291 (151/5182). AF 95% confidence interval is 0.0254. There are 2 homozygotes in gnomad4. There are 101 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPP4A	NM_001134225.2	c.1458T>C	p.Thr486=	synonymous_variant	15/25	ENST00000409851.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPP4A	ENST00000409851.8	c.1458T>C	p.Thr486=	synonymous_variant	15/25	1	NM_001134225.2

Frequencies

GnomAD3 genomes AF: 0.00111 AC: 169 AN: 152148 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0291

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00259 AC: 645 AN: 248708 Hom.: 13 AF XY: 0.00239 AC XY: 322 AN XY: 134972

Gnomad AFR exome AF: 0.0000648

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0348

Gnomad SAS exome AF: 0.000394

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000661

GnomAD4 exome AF: 0.000805 AC: 1176 AN: 1461476 Hom.: 19 Cov.: 31 AF XY: 0.000754 AC XY: 548 AN XY: 726990

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0247

Gnomad4 SAS exome AF: 0.000662

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00197

GnomAD4 genome AF: 0.00111 AC: 169 AN: 152266 Hom.: 2 Cov.: 33 AF XY: 0.00136 AC XY: 101 AN XY: 74468

Gnomad4 AFR AF: 0.000120

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0291

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000123 Hom.: 1

Bravo AF: 0.00149

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.088
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs74831847; hg19: chr2-99170844;