Genetic Variant IGBP1:p.Pro32Leu (chrX-70134042-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001551.3(IGBP1):c.95C>T(p.Pro32Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,097,162 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P32H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

IGBP1
NM_001551.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.18

Publications

0 publications found

Variant links:

Genes affected

IGBP1 (HGNC:5461): (immunoglobulin binding protein 1) The proliferation and differentiation of B cells is dependent upon a B-cell antigen receptor (BCR) complex. Binding of antigens to specific B-cell receptors results in a tyrosine phosphorylation reaction through the BCR complex and leads to multiple signal transduction pathways. [provided by RefSeq, Jul 2008]

IGBP1 Gene-Disease associations (from GenCC):

corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome
Inheritance: XL, Unknown, AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen

IGBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001551.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGBP1	NM_001551.3	MANE Select	c.95C>T	p.Pro32Leu	missense	Exon 2 of 7	NP_001542.1	P78318
IGBP1	NM_001370192.1		c.95C>T	p.Pro32Leu	missense	Exon 2 of 7	NP_001357121.1	P78318
IGBP1	NM_001370193.1		c.95C>T	p.Pro32Leu	missense	Exon 2 of 7	NP_001357122.1	P78318

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IGBP1	ENST00000356413.5	TSL:1 MANE Select	c.95C>T	p.Pro32Leu	missense	Exon 2 of 7	ENSP00000348784.4	P78318
IGBP1	ENST00000342206.10	TSL:1	c.95C>T	p.Pro32Leu	missense	Exon 1 of 6	ENSP00000363661.5	P78318
IGBP1	ENST00000937166.1		c.95C>T	p.Pro32Leu	missense	Exon 2 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.11e-7

AC:

AN:

1097162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

362522

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26383

American (AMR)

AF:

0.00

AC:

AN:

35203

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19380

East Asian (EAS)

AF:

0.00

AC:

AN:

30202

South Asian (SAS)

AF:

0.00

AC:

AN:

54121

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4131

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841151

Other (OTH)

AF:

0.00

AC:

AN:

46058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.85

M_CAP

Pathogenic

0.63

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.5

PhyloP100

5.2

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-7.8

REVEL

Benign

0.27

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

0.97

Vest4

0.22

MutPred

0.73

Gain of helix (P = 0.0325)

MVP

0.68

MPC

0.86

ClinPred

1.0

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.78

gMVP

0.50

Mutation Taster

=60/40

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over