Variant X-70146747-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_001551.3(IGBP1):c.597G>A(p.Arg199Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000844 in 1,203,166 control chromosomes in the GnomAD database, including 11 homozygotes. There are 335 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00095 ( 1 hom., 31 hem., cov: 22)

Exomes 𝑓: 0.00083 ( 10 hom. 304 hem. )

Consequence

IGBP1
NM_001551.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 2.08

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant X-70146747-G-A is Benign according to our data. Variant chrX-70146747-G-A is described in ClinVar as [Benign]. Clinvar id is 730942.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-70146747-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.08 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 31 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGBP1	NM_001551.3 linkuse as main transcript	c.597G>A	p.Arg199Arg	synonymous_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.597G>A	p.Arg199Arg	synonymous_variant	4/7	1	NM_001551.3	ENSP00000348784.4		P78318
IGBP1	ENST00000342206.10 linkuse as main transcript	c.597G>A	p.Arg199Arg	synonymous_variant	3/6	1		ENSP00000363661.5		P78318

Frequencies

GnomAD3 genomes

AF:

0.000951

AC:

105

AN:

110412

Hom.:

Cov.:

AF XY:

0.000951

AC XY:

AN XY:

32610

show subpopulations

Gnomad AFR

AF:

0.0000330

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000292

Gnomad ASJ

AF:

0.0361

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000755

Gnomad OTH

AF:

0.00135

GnomAD3 exomes

AF:

0.00170

AC:

311

AN:

183354

Hom.:

AF XY:

0.00159

AC XY:

108

AN XY:

67804

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.000474

Gnomad ASJ exome

AF:

0.0350

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.00309

GnomAD4 exome

AF:

0.000834

AC:

911

AN:

1092754

Hom.:

Cov.:

AF XY:

0.000849

AC XY:

304

AN XY:

358272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000625

Gnomad4 ASJ exome

AF:

0.0343

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000119

Gnomad4 OTH exome

AF:

0.00272

GnomAD4 genome

AF:

0.000951

AC:

105

AN:

110412

Hom.:

Cov.:

AF XY:

0.000951

AC XY:

AN XY:

32610

show subpopulations

Gnomad4 AFR

AF:

0.0000330

Gnomad4 AMR

AF:

0.000292

Gnomad4 ASJ

AF:

0.0361

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000755

Gnomad4 OTH

AF:

0.00135

Alfa

AF:

0.00486

Hom.:

Bravo

AF:

0.000952

EpiCase

AF:

0.000654

EpiControl

AF:

0.000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

IGBP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 07, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.6

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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