chrX-70134688-C-G

Variant names:

• chrX-70134688-C-G
• rs1470339139
• NM_001551.3:c.354C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001551.3(IGBP1):​c.354C>G​(p.Cys118Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 1 hem.)
  • Failed GnomAD Quality Control
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.396
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25673187).

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.354C>G	p.Cys118Trp	missense	Exon 3 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.354C>G	p.Cys118Trp	missense	Exon 3 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.354C>G	p.Cys118Trp	missense	Exon 3 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.354C>G	p.Cys118Trp	missense	Exon 3 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.354C>G	p.Cys118Trp	missense	Exon 2 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.354C>G	p.Cys118Trp	missense	Exon 3 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.11e-7 AC: 1 AN: 1097308 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 1 AN XY: 362682

African (AFR) AF: 0.00 AC: 0 AN: 26390

American (AMR) AF: 0.00 AC: 0 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30199

South Asian (SAS) AF: 0.00 AC: 0 AN: 54128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841265

Other (OTH) AF: 0.0000217 AC: 1 AN: 46069

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.18	T
M_CAP	Pathogenic	0.31	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.40
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.054
Sift	Benign	0.14	T
Sift4G	Benign	0.18	T
Polyphen		0.47	P
Vest4		0.27
MutPred		0.28		Loss of catalytic residue at H120 (P = 0.1407)
MVP		0.50
MPC		0.70
ClinPred		0.18	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.26
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1470339139; hg19: chrX-69354538;