chr11-72225032-C-T

Variant names:

• chr11-72225032-C-T
• rs2135413784
• NM_001567.4:c.48C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001567.4(INPPL1):​c.48C>T​(p.Ser16Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: INPPL1 NM_001567.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.710
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 11-72225032-C-T is Benign according to our data. Variant chr11-72225032-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1545584.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.71 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.48C>T	p.Ser16Ser	synonymous	Exon 1 of 28	NP_001558.3
	INPPL1	NM_001440434.1		c.48C>T	p.Ser16Ser	synonymous	Exon 1 of 28	NP_001427363.1
	INPPL1	NM_001440435.1		c.48C>T	p.Ser16Ser	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.48C>T	p.Ser16Ser	synonymous	Exon 1 of 28	ENSP00000298229.2	O15357-1
	INPPL1	ENST00000924957.1		c.48C>T	p.Ser16Ser	synonymous	Exon 2 of 29	ENSP00000595016.1
	INPPL1	ENST00000946902.1		c.48C>T	p.Ser16Ser	synonymous	Exon 2 of 29	ENSP00000616961.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000186 AC: 2 AN: 1073582 Hom.: 0 Cov.: 30 AF XY: 0.00000394 AC XY: 2 AN XY: 507652

African (AFR) AF: 0.00 AC: 0 AN: 22544

American (AMR) AF: 0.00 AC: 0 AN: 8122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13920

East Asian (EAS) AF: 0.00 AC: 0 AN: 26034

South Asian (SAS) AF: 0.00 AC: 0 AN: 19668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 21016

Middle Eastern (MID) AF: 0.000346 AC: 1 AN: 2892

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 916386

Other (OTH) AF: 0.0000233 AC: 1 AN: 43000

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		0.71
PromoterAI		-0.063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2135413784; hg19: chr11-71936076;