chrX-70146711-G-C

Position:

• chrX-70146711-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001551.3(IGBP1):​c.561G>C​(p.Glu187Asp) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.307

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39207545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGBP1	NM_001551.3	c.561G>C	p.Glu187Asp	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	c.561G>C	p.Glu187Asp	missense_variant	4/7	1	NM_001551.3	ENSP00000348784.4
IGBP1	ENST00000342206.10	c.561G>C	p.Glu187Asp	missense_variant	3/6	1		ENSP00000363661.5

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.15e-7 AC: 1 AN: 1092693 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 358197

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 0.0000218

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.561G>C (p.E187D) alteration is located in exon 4 (coding exon 3) of the IGBP1 gene. This alteration results from a G to C substitution at nucleotide position 561, causing the glutamic acid (E) at amino acid position 187 to be replaced by an aspartic acid (D). 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.0
DANN	Uncertain	0.99
DEOGEN2	Benign	0.035	T;T
FATHMM_MKL	Benign	0.098	N
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.12
Sift	Benign	0.15	T;T
Sift4G	Benign	0.17	T;T
Polyphen		0.41	B;B
Vest4		0.31
MutPred		0.76		Loss of disorder (P = 0.195);Loss of disorder (P = 0.195);
MVP		0.73
MPC		0.50
ClinPred		0.54	D
GERP RS		1.4
Varity_R		0.26
gMVP		0.42

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: rs2085168913; hg19: chrX-69366561;