X-70133952-C-G

Variant names:

• chrX-70133952-C-G
• NM_001551.3:c.5C>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_001551.3(IGBP1):​c.5C>G​(p.Ala2Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.56

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 4 ACMG points.

• PM1: In a modified_residue N-acetylalanine (size 0) in uniprot entity IGBP1_HUMAN
• 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.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 7	ENST00000356413.5	NP_001542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGBP1	ENST00000356413.5	c.5C>G	p.Ala2Gly	missense_variant	Exon 2 of 7	1	NM_001551.3	ENSP00000348784.4
IGBP1	ENST00000342206.10	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 6	1		ENSP00000363661.5

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 30, 2017

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The IGBP1 c.5C>G (p.Ala2Gly) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in the Genome Aggregation Database despite its location in a region of good sequencing coverage, which suggests the variant is rare. Based on the available information, the p.Ala2Gly variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.031	T;T
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.50	.;T
M_CAP	Pathogenic	0.42	D
MetaRNN	Uncertain	0.54	D;D
MetaSVM	Benign	-0.76	T
MutationAssessor	Pathogenic	2.9	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.8	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.020	D;D
Polyphen		0.96	D;D
Vest4		0.35
MutPred		0.14		Gain of relative solvent accessibility (P = 0.1571);Gain of relative solvent accessibility (P = 0.1571);
MVP		0.70
MPC		0.88
ClinPred		0.95	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.25
gMVP		0.093

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-69353802;