rs1412238750

Variant names:

• chrX-70148797-C-T
• rs1412238750
• NM_001551.3:c.715C>T
• IGBP1 p.Pro239Ser

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 1 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGBP1	NM_001551.3	MANE Select	c.715C>T	p.Pro239Ser	missense	Exon 5 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.715C>T	p.Pro239Ser	missense	Exon 5 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.715C>T	p.Pro239Ser	missense	Exon 5 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.715C>T	p.Pro239Ser	missense	Exon 5 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.715C>T	p.Pro239Ser	missense	Exon 4 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.715C>T	p.Pro239Ser	missense	Exon 5 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000550 AC: 1 AN: 181949 AF XY: 0.00

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 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

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

American (AMR) AF: 0.0000284 AC: 1 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: 0.00 AC: 0 AN: 836304

Other (OTH) AF: 0.0000436 AC: 2 AN: 45891

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	not specified (2)

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Pathogenic	0.44	D
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.40	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		4.6
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.26
Sift	Benign	0.043	D
Sift4G	Uncertain	0.0090	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.53
gMVP		0.78
Mutation Taster		=66/34	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1412238750;

hg19: chrX-69368647;

COSMIC: COSV104415958;