11-72225386-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001567.4(INPPL1):c.182+220A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 985,378 control chromosomes in the GnomAD database, including 237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (68 hom., cov: 32)
  • Exomes 𝑓: 0.020 (169 hom.)
• Consequence: INPPL1 NM_001567.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.905

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=-0.81).
• BP6: Variant 11-72225386-A-G is Benign according to our data. Variant chr11-72225386-A-G is described in ClinVar as [Benign]. Clinvar id is 1237230.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0199 (3029/152270) while in subpopulation NFE AF= 0.0241 (1637/68020). AF 95% confidence interval is 0.0231. There are 68 homozygotes in gnomad4. There are 1662 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
INPPL1	NM_001567.4	c.182+220A>G		intron_variant		ENST00000298229.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
INPPL1	ENST00000298229.7	c.182+220A>G		intron_variant		1	NM_001567.4	P1
INPPL1	ENST00000541544.1	n.98+220A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0199 AC: 3027 AN: 152152 Hom.: 67 Cov.: 32

Gnomad AFR AF: 0.00434

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.0158

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0241

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.0203 AC: 16934 AN: 833108 Hom.: 169 Cov.: 30 AF XY: 0.0200 AC XY: 7706 AN XY: 384714

Gnomad4 AFR exome AF: 0.00336

Gnomad4 AMR exome AF: 0.0102

Gnomad4 ASJ exome AF: 0.0225

Gnomad4 EAS exome AF: 0.0132

Gnomad4 SAS exome AF: 0.0125

Gnomad4 FIN exome AF: 0.0652

Gnomad4 NFE exome AF: 0.0210

Gnomad4 OTH exome AF: 0.0174

GnomAD4 genome AF: 0.0199 AC: 3029 AN: 152270 Hom.: 68 Cov.: 32 AF XY: 0.0223 AC XY: 1662 AN XY: 74446

Gnomad4 AFR AF: 0.00433

Gnomad4 AMR AF: 0.00738

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.0159

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.0756

Gnomad4 NFE AF: 0.0241

Gnomad4 OTH AF: 0.0151

Alfa AF: 0.0280 Hom.: 17

Bravo AF: 0.0137

Asia WGS AF: 0.0130 AC: 45 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

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	12
Dann	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs117062675; hg19: chr11-71936430;