Variant rs1412238750 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001551.3(IGBP1):c.715C>T(p.Pro239Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,091,619 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )

Consequence

IGBP1
NM_001551.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 4.61

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 links:

IGBP1-AS2 (HGNC:):

IGBP1-AS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGBP1	NM_001551.3 linkuse as main transcript	c.715C>T	p.Pro239Ser	missense_variant	5/7	ENST00000356413.5	NP_001542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IGBP1	ENST00000356413.5 linkuse as main transcript	c.715C>T	p.Pro239Ser	missense_variant	5/7	1	NM_001551.3	ENSP00000348784.4	P78318
IGBP1	ENST00000342206.10 linkuse as main transcript	c.715C>T	p.Pro239Ser	missense_variant	4/6	1		ENSP00000363661.5	P78318
IGBP1-AS2	ENST00000403371.2 linkuse as main transcript	n.298G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000550

AC:

AN:

181949

Hom.:

AF XY:

0.00

AC XY:

AN XY:

66451

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1091619

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

357233

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000436

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Ambry Genetics	Jul 13, 2021	The c.715C>T (p.P239S) alteration is located in exon 5 (coding exon 4) of the IGBP1 gene. This alteration results from a C to T substitution at nucleotide position 715, causing the proline (P) at amino acid position 239 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Uncertain significance, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Mar 03, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

.;T

M_CAP

Pathogenic

0.44

MetaRNN

Uncertain

0.67

D;D

MetaSVM

Benign

-0.40

MutationAssessor

Pathogenic

3.1

M;M

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.26

Sift

Benign

0.043

D;D

Sift4G

Uncertain

0.0090

D;D

Polyphen

0.90

P;P

Vest4

0.36

MutPred

0.60

Loss of catalytic residue at P238 (P = 0.0121);Loss of catalytic residue at P238 (P = 0.0121);

MVP

0.70

MPC

1.1

ClinPred

0.96

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over