X-70148797-C-T

Variant names:

• chrX-70148797-C-T
• rs1412238750
• NM_001551.3:c.715C>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001551.3(IGBP1):​c.715C>T​(p.Pro239Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000275 in 1,091,619 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.61

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-AS2 (HGNC:40294): (IGBP1 antisense RNA 2)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGBP1	NM_001551.3	c.715C>T	p.Pro239Ser	missense_variant	Exon 5 of 7	ENST00000356413.5	NP_001542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGBP1	ENST00000356413.5	c.715C>T	p.Pro239Ser	missense_variant	Exon 5 of 7	1	NM_001551.3	ENSP00000348784.4
IGBP1	ENST00000342206.10	c.715C>T	p.Pro239Ser	missense_variant	Exon 4 of 6	1		ENSP00000363661.5
IGBP1-AS2	ENST00000403371.2	n.298G>A		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.00000550 AC: 1 AN: 181949 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66451

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 3 AN: 1091619 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 357233

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000436

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:2

Mar 03, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 13, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.715C>T (p.P239S) alteration is located in exon 5 (coding exon 4) of the IGBP1 gene. This alteration results from a C to T substitution at nucleotide position 715, causing the proline (P) at amino acid position 239 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	.;T
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.67	D;D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.1	M;M
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.5	D;D
REVEL	Benign	0.26
Sift	Benign	0.043	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.90	P;P
Vest4		0.36
MutPred		0.60		Loss of catalytic residue at P238 (P = 0.0121);Loss of catalytic residue at P238 (P = 0.0121);
MVP		0.70
MPC		1.1
ClinPred		0.96	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.78

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

Other links and lift over

dbSNP: rs1412238750; hg19: chrX-69368647; COSMIC: COSV104415958;