Variant chrX-70134651-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001551.3(IGBP1):c.317G>A(p.Arg106Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00135 in 1,210,547 control chromosomes in the GnomAD database, including 5 homozygotes. There are 537 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., 39 hem., cov: 24)

Exomes 𝑓: 0.0013 ( 5 hom. 498 hem. )

Consequence

IGBP1
NM_001551.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 6.78

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009251326).

BP6

Variant X-70134651-G-A is Benign according to our data. Variant chrX-70134651-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 93780.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-70134651-G-A is described in Lovd as [Benign].

BS2

High Hemizygotes in GnomAd4 at 39 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGBP1	NM_001551.3 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/7	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.317G>A	p.Arg106Gln	missense_variant	3/7	1	NM_001551.3	ENSP00000348784.4		P78318
IGBP1	ENST00000342206.10 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	2/6	1		ENSP00000363661.5		P78318

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

161

AN:

112366

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

34518

show subpopulations

Gnomad AFR

AF:

0.000162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000282

Gnomad ASJ

AF:

0.0260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.00265

GnomAD3 exomes

AF:

0.00180

AC:

330

AN:

183475

Hom.:

AF XY:

0.00180

AC XY:

122

AN XY:

67903

show subpopulations

Gnomad AFR exome

AF:

0.000228

Gnomad AMR exome

AF:

0.000438

Gnomad ASJ exome

AF:

0.0262

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000187

Gnomad NFE exome

AF:

0.00122

Gnomad OTH exome

AF:

0.00353

GnomAD4 exome

AF:

0.00134

AC:

1469

AN:

1098126

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

498

AN XY:

363480

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.000483

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000321

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00143

AC:

161

AN:

112421

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

AN XY:

34583

show subpopulations

Gnomad4 AFR

AF:

0.000161

Gnomad4 AMR

AF:

0.000282

Gnomad4 ASJ

AF:

0.0260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.00262

Alfa

AF:

0.00413

Hom.:

Bravo

AF:

0.00133

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00138

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00253

AC:

ExAC

AF:

0.00161

AC:

195

EpiCase

AF:

0.00180

EpiControl

AF:

0.00231

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Jul 17, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 30, 2013	- -

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.017

T;T

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

.;T

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.0093

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

M;M

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.23

Sift

Uncertain

0.0090

D;D

Sift4G

Benign

0.17

T;T

Polyphen

0.84

P;P

Vest4

0.33

MVP

0.68

MPC

0.71

ClinPred

0.029

GERP RS

4.9

Varity_R

0.73

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