Genetic Variant NM_001567.4:c.36C>A (chr11-72225020-C-A) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1

The NM_001567.4(INPPL1):c.36C>A(p.Gly12Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000649 in 1,217,468 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

INPPL1
NM_001567.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.234

Publications

0 publications found

Variant links:

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

INPPL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 11-72225020-C-A is Benign according to our data. Variant chr11-72225020-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1101041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.234 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000284 (43/151218) while in subpopulation AFR AF = 0.00102 (42/41284). AF 95% confidence interval is 0.000773. There are 1 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
INPPL1	NM_001567.4	MANE Select	c.36C>A	p.Gly12Gly	synonymous	Exon 1 of 28	NP_001558.3
INPPL1	NM_001440434.1		c.36C>A	p.Gly12Gly	synonymous	Exon 1 of 28	NP_001427363.1
INPPL1	NM_001440435.1		c.36C>A	p.Gly12Gly	synonymous	Exon 2 of 29	NP_001427364.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
INPPL1	ENST00000298229.7	TSL:1 MANE Select	c.36C>A	p.Gly12Gly	synonymous	Exon 1 of 28	ENSP00000298229.2	O15357-1
INPPL1	ENST00000924957.1		c.36C>A	p.Gly12Gly	synonymous	Exon 2 of 29	ENSP00000595016.1
INPPL1	ENST00000946902.1		c.36C>A	p.Gly12Gly	synonymous	Exon 2 of 29	ENSP00000616961.1

Frequencies

GnomAD3 genomes

AF:

0.000284

AC:

AN:

151218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000338

AC:

AN:

1066250

Hom.:

Cov.:

AF XY:

0.0000199

AC XY:

AN XY:

503722

show subpopulations

African (AFR)

AF:

0.00157

AC:

AN:

22280

American (AMR)

AF:

0.00

AC:

AN:

7864

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13588

East Asian (EAS)

AF:

0.00

AC:

AN:

25404

South Asian (SAS)

AF:

0.00

AC:

AN:

19510

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2856

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

911440

Other (OTH)

AF:

0.0000235

AC:

AN:

42504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000284

AC:

AN:

151218

Hom.:

Cov.:

AF XY:

0.000325

AC XY:

AN XY:

73864

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

41284

American (AMR)

AF:

0.0000658

AC:

AN:

15198

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10274

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67744

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000344

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Opsismodysplasia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.23

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=300/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over