Variant X-70146758-T-C 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.608T>C(p.Ile203Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,172,798 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,952 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 4 hom., 98 hem., cov: 22)

Exomes 𝑓: 0.0058 ( 7 hom. 1854 hem. )

Consequence

IGBP1
NM_001551.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.49

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=0.010424465).

BP6

Variant X-70146758-T-C is Benign according to our data. Variant chrX-70146758-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 499182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes 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.608T>C	p.Ile203Thr	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.608T>C	p.Ile203Thr	missense_variant	4/7	1	NM_001551.3	ENSP00000348784.4		P78318
IGBP1	ENST00000342206.10 linkuse as main transcript	c.608T>C	p.Ile203Thr	missense_variant	3/6	1		ENSP00000363661.5		P78318

Frequencies

GnomAD3 genomes

AF:

0.00345

AC:

381

AN:

110490

Hom.:

Cov.:

AF XY:

0.00300

AC XY:

AN XY:

32714

show subpopulations

Gnomad AFR

AF:

0.000626

Gnomad AMI

AF:

0.00146

Gnomad AMR

AF:

0.00126

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00524

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00596

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.00361

AC:

641

AN:

177726

Hom.:

AF XY:

0.00370

AC XY:

235

AN XY:

63518

show subpopulations

Gnomad AFR exome

AF:

0.000508

Gnomad AMR exome

AF:

0.000808

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000324

Gnomad FIN exome

AF:

0.00552

Gnomad NFE exome

AF:

0.00635

Gnomad OTH exome

AF:

0.00406

GnomAD4 exome

AF:

0.00580

AC:

6163

AN:

1062253

Hom.:

Cov.:

AF XY:

0.00549

AC XY:

1854

AN XY:

337517

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.000941

Gnomad4 ASJ exome

AF:

0.000210

Gnomad4 EAS exome

AF:

0.0000335

Gnomad4 SAS exome

AF:

0.000529

Gnomad4 FIN exome

AF:

0.00621

Gnomad4 NFE exome

AF:

0.00693

Gnomad4 OTH exome

AF:

0.00397

GnomAD4 genome

AF:

0.00346

AC:

382

AN:

110545

Hom.:

Cov.:

AF XY:

0.00299

AC XY:

AN XY:

32779

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00126

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000387

Gnomad4 FIN

AF:

0.00524

Gnomad4 NFE

AF:

0.00596

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.00148

Hom.:

Bravo

AF:

0.00306

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00658

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00654

AC:

ExAC

AF:

0.0179

AC:

2171

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Jan 06, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.010

T;T

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.67

.;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.055

Sift

Benign

0.41

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.0010

B;B

Vest4

0.078

MPC

0.55

ClinPred

0.0031

GERP RS

4.0

Varity_R

0.064

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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