rs11548491

Variant names:

• chr11-72237492-C-G
• rs11548491
• NM_001567.4:c.3248C>G

Your query was ambiguous. Multiple possible variants found:

• chr11-72237492-C-G
• chr11-72237492-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001567.4(INPPL1):​c.3248C>G​(p.Ala1083Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 1,609,176 control chromosomes in the GnomAD database, including 6,584 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1849 hom., cov: 33)
  • Exomes 𝑓: 0.071 (4735 hom.)
• Consequence: INPPL1 NM_001567.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.335
• Publications: 22 publications found

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]

INPPL1 Gene-Disease associations (from GenCC):

• opsismodysplasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• schneckenbecken dysplasia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003971219).
• BP6: Variant 11-72237492-C-G is Benign according to our data. Variant chr11-72237492-C-G is described in ClinVar as Benign. ClinVar VariationId is 1170425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001567.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPPL1	NM_001567.4	MANE Select	c.3248C>G	p.Ala1083Gly	missense	Exon 26 of 28	NP_001558.3
	INPPL1	NM_001440434.1		c.3314C>G	p.Ala1105Gly	missense	Exon 26 of 28	NP_001427363.1
	INPPL1	NM_001440435.1		c.3248C>G	p.Ala1083Gly	missense	Exon 27 of 29	NP_001427364.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INPPL1	ENST00000298229.7	TSL:1 MANE Select	c.3248C>G	p.Ala1083Gly	missense	Exon 26 of 28	ENSP00000298229.2	O15357-1
	INPPL1	ENST00000538751.5	TSL:1	c.2522C>G	p.Ala841Gly	missense	Exon 25 of 27	ENSP00000444619.1	O15357-2
	INPPL1	ENST00000924957.1		c.3263C>G	p.Ala1088Gly	missense	Exon 27 of 29	ENSP00000595016.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19632 AN: 152124 Hom.: 1846 Cov.: 33

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0922

Gnomad ASJ AF: 0.0910

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0836

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0619

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.0964 AC: 23623 AN: 245048 AF XY: 0.0913

Gnomad AFR exome AF: 0.273

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.0775

Gnomad EAS exome AF: 0.154

Gnomad FIN exome AF: 0.108

Gnomad NFE exome AF: 0.0615

Gnomad OTH exome AF: 0.0881

GnomAD4 exome AF: 0.0710 AC: 103467 AN: 1456932 Hom.: 4735 Cov.: 32 AF XY: 0.0703 AC XY: 50881 AN XY: 724052

African (AFR) AF: 0.274 AC: 9153 AN: 33402

American (AMR) AF: 0.110 AC: 4876 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 1961 AN: 26048

East Asian (EAS) AF: 0.124 AC: 4900 AN: 39554

South Asian (SAS) AF: 0.0817 AC: 7032 AN: 86034

European-Finnish (FIN) AF: 0.103 AC: 5398 AN: 52312

Middle Eastern (MID) AF: 0.0816 AC: 469 AN: 5746

European-Non Finnish (NFE) AF: 0.0584 AC: 64798 AN: 1109178

Other (OTH) AF: 0.0811 AC: 4880 AN: 60152

GnomAD4 genome AF: 0.129 AC: 19654 AN: 152244 Hom.: 1849 Cov.: 33 AF XY: 0.129 AC XY: 9633 AN XY: 74430

African (AFR) AF: 0.266 AC: 11043 AN: 41526

American (AMR) AF: 0.0921 AC: 1409 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0910 AC: 316 AN: 3472

East Asian (EAS) AF: 0.159 AC: 819 AN: 5164

South Asian (SAS) AF: 0.0833 AC: 402 AN: 4828

European-Finnish (FIN) AF: 0.110 AC: 1164 AN: 10618

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0619 AC: 4211 AN: 68010

Other (OTH) AF: 0.105 AC: 223 AN: 2114

Alfa AF: 0.0468 Hom.: 87

Bravo AF: 0.133

TwinsUK AF: 0.0593 AC: 220

ALSPAC AF: 0.0550 AC: 212

ESP6500AA AF: 0.252 AC: 1109

ESP6500EA AF: 0.0584 AC: 501

ExAC AF: 0.0976 AC: 11834

Asia WGS AF: 0.105 AC: 364 AN: 3478

EpiCase AF: 0.0598

EpiControl AF: 0.0589

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	8.5
DANN	Benign	0.61
DEOGEN2	Benign	0.35	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0040	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.44	N
PhyloP100		0.34
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.090	N
REVEL	Benign	0.18
Sift	Benign	0.60	T
Sift4G	Benign	0.38	T
Polyphen		0.0	B
Vest4		0.042
MPC		0.11
ClinPred		0.00011	T
GERP RS		2.6
PromoterAI		-0.0054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.16
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11548491; hg19: chr11-71948536; COSMIC: COSV53355328; COSMIC: COSV53355328;