11-72224911-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001567.4(INPPL1):c.-74G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00917 in 991,432 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (26 hom., cov: 31)
  • Exomes 𝑓: 0.0088 (46 hom.)
• Consequence: INPPL1 NM_001567.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.531

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-72224911-G-C is Benign according to our data. Variant chr11-72224911-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1188591.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPPL1	NM_001567.4	c.-74G>C		5_prime_UTR_variant	1/28	ENST00000298229.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPPL1	ENST00000298229.7	c.-74G>C		5_prime_UTR_variant	1/28	1	NM_001567.4	P1
INPPL1	ENST00000540973.1	c.-74G>C		5_prime_UTR_variant	2/2	3
INPPL1	ENST00000543234.1	c.-74G>C		5_prime_UTR_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1677 AN: 151318 Hom.: 26 Cov.: 31

Gnomad AFR AF: 0.00162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0156

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.0124

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00952

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00883 AC: 7416 AN: 840008 Hom.: 46 Cov.: 13 AF XY: 0.00869 AC XY: 3416 AN XY: 392966

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.00610

Gnomad4 EAS exome AF: 0.0639

Gnomad4 SAS exome AF: 0.0103

Gnomad4 FIN exome AF: 0.0251

Gnomad4 NFE exome AF: 0.00825

Gnomad4 OTH exome AF: 0.0129

GnomAD4 genome AF: 0.0111 AC: 1674 AN: 151424 Hom.: 26 Cov.: 31 AF XY: 0.0118 AC XY: 875 AN XY: 74020

Gnomad4 AFR AF: 0.00162

Gnomad4 AMR AF: 0.0155

Gnomad4 ASJ AF: 0.00922

Gnomad4 EAS AF: 0.0674

Gnomad4 SAS AF: 0.0122

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.00949

Gnomad4 OTH AF: 0.0124

Alfa AF: 0.00963 Hom.: 2

Bravo AF: 0.0106

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	12
Dann	Benign	0.86

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: rs368831164; hg19: chr11-71935955;