rs1412238750

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-70148797-C-G
• chrX-70148797-C-T

Variant summary

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

The NM_001551.3(IGBP1):​c.715C>G​(p.Pro239Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000916 in 1,091,620 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P239S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.61
• 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-AS2 (HGNC:40294): (IGBP1 antisense RNA 2)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGBP1	NM_001551.3	MANE Select	c.715C>G	p.Pro239Ala	missense	Exon 5 of 7	NP_001542.1
	IGBP1	NM_001370192.1		c.715C>G	p.Pro239Ala	missense	Exon 5 of 7	NP_001357121.1
	IGBP1	NM_001370193.1		c.715C>G	p.Pro239Ala	missense	Exon 5 of 7	NP_001357122.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGBP1	ENST00000356413.5	TSL:1 MANE Select	c.715C>G	p.Pro239Ala	missense	Exon 5 of 7	ENSP00000348784.4
	IGBP1	ENST00000342206.10	TSL:1	c.715C>G	p.Pro239Ala	missense	Exon 4 of 6	ENSP00000363661.5
	IGBP1-AS2	ENST00000403371.2	TSL:3	n.298G>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.16e-7 AC: 1 AN: 1091620 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 357234

African (AFR) AF: 0.00 AC: 0 AN: 26292

American (AMR) AF: 0.00 AC: 0 AN: 35187

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19328

East Asian (EAS) AF: 0.00 AC: 0 AN: 30177

South Asian (SAS) AF: 0.00 AC: 0 AN: 53825

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40497

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4118

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 836305

Other (OTH) AF: 0.00 AC: 0 AN: 45891

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.056
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		4.6
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.27
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.015	D
Polyphen		0.99	D
Vest4		0.28
MutPred		0.60		Loss of catalytic residue at P238 (P = 0.0121)
MVP		0.74
MPC		1.0
ClinPred		0.99	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.69
Mutation Taster		=56/44	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: rs1412238750; hg19: chrX-69368647;