rs368773089

Variant names:

• chrX-70146686-T-C
• rs368773089
• NM_001551.3:c.536T>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2 B:2
• Conservation: PhyloP100: 6.87
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome

  Inheritance: XL, Unknown, AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2177378).
• BS2: High AC in GnomAd4 at 9 XL,Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001551.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGBP1	NM_001551.3	MANE Select	c.536T>C	p.Val179Ala	missense	Exon 4 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.536T>C	p.Val179Ala	missense	Exon 4 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.536T>C	p.Val179Ala	missense	Exon 4 of 7	NP_001357122.1	P78318

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGBP1	ENST00000356413.5	TSL:1 MANE Select	c.536T>C	p.Val179Ala	missense	Exon 4 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.536T>C	p.Val179Ala	missense	Exon 3 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.536T>C	p.Val179Ala	missense	Exon 4 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes AF: 0.0000823 AC: 9 AN: 109340 Hom.: 0 Cov.: 21

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

GnomAD2 exomes AF: 0.0000491 AC: 9 AN: 183251 AF XY: 0.0000885

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000979

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000365 AC: 40 AN: 1094975 Hom.: 0 Cov.: 29 AF XY: 0.0000555 AC XY: 20 AN XY: 360457

African (AFR) AF: 0.00 AC: 0 AN: 26339

American (AMR) AF: 0.00 AC: 0 AN: 35194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19364

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.000969 AC: 4 AN: 4127

European-Non Finnish (NFE) AF: 0.0000334 AC: 28 AN: 839166

Other (OTH) AF: 0.000174 AC: 8 AN: 45979

GnomAD4 genome AF: 0.0000823 AC: 9 AN: 109340 Hom.: 0 Cov.: 21 AF XY: 0.000126 AC XY: 4 AN XY: 31678

African (AFR) AF: 0.00 AC: 0 AN: 30042

American (AMR) AF: 0.00 AC: 0 AN: 10096

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2618

East Asian (EAS) AF: 0.00 AC: 0 AN: 3444

South Asian (SAS) AF: 0.00 AC: 0 AN: 2509

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5563

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 233

European-Non Finnish (NFE) AF: 0.000152 AC: 8 AN: 52679

Other (OTH) AF: 0.000677 AC: 1 AN: 1478

Alfa AF: 0.000130 Hom.: 1

Bravo AF: 0.0000642

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000446 AC: 3

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	1	-	IGBP1-related disorder (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		6.9
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.18
Sift	Benign	0.082	T
Sift4G	Benign	0.27	T
Polyphen		0.073	B
Vest4		0.36
MVP		0.76
MPC		0.56
ClinPred		0.21	T
GERP RS		5.1
Varity_R		0.69
gMVP		0.49
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

dbSNP: rs368773089; hg19: chrX-69366536;