chrX-70146686-T-C

Position:

chrX-70146686-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001551.3(IGBP1):c.536T>C(p.Val179Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000407 in 1,204,315 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000082 ( 0 hom., 4 hem., cov: 21)

Exomes 𝑓: 0.000037 ( 0 hom. 20 hem. )

Consequence

IGBP1
NM_001551.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.87

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2177378).

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGBP1	NM_001551.3 linkuse as main transcript	c.536T>C	p.Val179Ala	missense_variant	4/7	ENST00000356413.5	NP_001542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGBP1	ENST00000356413.5 linkuse as main transcript	c.536T>C	p.Val179Ala	missense_variant	4/7	1	NM_001551.3	ENSP00000348784.4		P78318
IGBP1	ENST00000342206.10 linkuse as main transcript	c.536T>C	p.Val179Ala	missense_variant	3/6	1		ENSP00000363661.5		P78318

Frequencies

GnomAD3 genomes

AF:

0.0000823

AC:

AN:

109340

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

31678

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000152

Gnomad OTH

AF:

0.000677

GnomAD3 exomes

AF:

0.0000491

AC:

AN:

183251

Hom.:

AF XY:

0.0000885

AC XY:

AN XY:

67779

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000979

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000365

AC:

AN:

1094975

Hom.:

Cov.:

AF XY:

0.0000555

AC XY:

AN XY:

360457

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000334

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.0000823

AC:

AN:

109340

Hom.:

Cov.:

AF XY:

0.000126

AC XY:

AN XY:

31678

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000152

Gnomad4 OTH

AF:

0.000677

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2023

The c.536T>C (p.V179A) alteration is located in exon 4 (coding exon 3) of the IGBP1 gene. This alteration results from a T to C substitution at nucleotide position 536, causing the valine (V) at amino acid position 179 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

IGBP1-related disorder

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 27, 2022

The IGBP1 c.536T>C variant is predicted to result in the amino acid substitution p.Val179Ala. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0097% of alleles in individuals of European (Non-Finnish) descent in gnomAD, including seven hemizygous individuals (http://gnomad.broadinstitute.org/variant/X-69366536-T-C). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.085

T;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.60

.;T

M_CAP

Benign

0.0083

MetaRNN

Benign

0.22

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.18

Sift

Benign

0.082

T;T

Sift4G

Benign

0.27

T;T

Polyphen

0.073

B;B

Vest4

0.36

MVP

0.76

MPC

0.56

ClinPred

0.21

GERP RS

5.1

Varity_R

0.69

gMVP

0.49

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