11-72230337-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001567.4(INPPL1):c.1091-25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 1,613,394 control chromosomes in the GnomAD database, including 54,263 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (10116 hom., cov: 33)
  • Exomes 𝑓: 0.23 (44147 hom.)
• Consequence: INPPL1 NM_001567.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.252

Genes affected

INPPL1 (HGNC:6080): (inositol polyphosphate phosphatase like 1) The protein encoded by this gene is an SH2-containing 5'-inositol phosphatase that is involved in the regulation of insulin function. The encoded protein also plays a role in the regulation of epidermal growth factor receptor turnover and actin remodelling. Additionally, this gene supports metastatic growth in breast cancer and is a valuable biomarker for breast cancer. [provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-72230337-A-G is Benign according to our data. Variant chr11-72230337-A-G is described in ClinVar as [Benign]. Clinvar id is 1289494.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPPL1	NM_001567.4	c.1091-25A>G		intron_variant		ENST00000298229.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPPL1	ENST00000298229.7	c.1091-25A>G		intron_variant		1	NM_001567.4	P1
INPPL1	ENST00000538751.5	c.365-25A>G		intron_variant		1
INPPL1	ENST00000540329.5	c.275-25A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49533 AN: 152104 Hom.: 10093 Cov.: 33

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.278

GnomAD3 exomes AF: 0.279 AC: 69816 AN: 250574 Hom.: 11378 AF XY: 0.277 AC XY: 37485 AN XY: 135442

Gnomad AFR exome AF: 0.583

Gnomad AMR exome AF: 0.271

Gnomad ASJ exome AF: 0.187

Gnomad EAS exome AF: 0.403

Gnomad SAS exome AF: 0.394

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.231 AC: 337976 AN: 1461172 Hom.: 44147 Cov.: 35 AF XY: 0.235 AC XY: 170674 AN XY: 726910

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.268

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.354

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.326 AC: 49607 AN: 152222 Hom.: 10116 Cov.: 33 AF XY: 0.328 AC XY: 24416 AN XY: 74420

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.218

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.284

Alfa AF: 0.253 Hom.: 1163

Bravo AF: 0.338

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 19, 2018

- -

Opsismodysplasia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.9
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2276047; hg19: chr11-71941381;