11-72225020-C-T

Variant names:

• chr11-72225020-C-T
• rs1011212998
• NM_001567.4:c.36C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001567.4(INPPL1):​c.36C>T​(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000938 in 1,066,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G12G) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: INPPL1 NM_001567.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP7: Synonymous conserved (PhyloP=0.234 with no splicing effect.

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.36C>T	p.Gly12Gly	synonymous	Exon 1 of 28	NP_001558.3
	INPPL1	NM_001440434.1		c.36C>T	p.Gly12Gly	synonymous	Exon 1 of 28	NP_001427363.1
	INPPL1	NM_001440435.1		c.36C>T	p.Gly12Gly	synonymous	Exon 2 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.36C>T	p.Gly12Gly	synonymous	Exon 1 of 28	ENSP00000298229.2	O15357-1
	INPPL1	ENST00000924957.1		c.36C>T	p.Gly12Gly	synonymous	Exon 2 of 29	ENSP00000595016.1
	INPPL1	ENST00000946902.1		c.36C>T	p.Gly12Gly	synonymous	Exon 2 of 29	ENSP00000616961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.38e-7 AC: 1 AN: 1066250 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 503722

African (AFR) AF: 0.00 AC: 0 AN: 22280

American (AMR) AF: 0.00 AC: 0 AN: 7864

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13588

East Asian (EAS) AF: 0.00 AC: 0 AN: 25404

South Asian (SAS) AF: 0.00 AC: 0 AN: 19510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2856

European-Non Finnish (NFE) AF: 0.00000110 AC: 1 AN: 911440

Other (OTH) AF: 0.00 AC: 0 AN: 42504

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.23
PromoterAI		-0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

Other links and lift over

dbSNP: rs1011212998; hg19: chr11-71936064;