X-70133893-T-A

Position:

• chrX-70133893-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001370192.1(IGBP1):​c.-50-5T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,100,701 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 4 hem., cov: 24)
  • Exomes 𝑓: 0.000048 (0 hom. 12 hem.)
• Consequence: IGBP1 NM_001370192.1 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.429

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-70133893-T-A is Benign according to our data. Variant chrX-70133893-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660802.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGBP1	NM_001551.3	c.-55T>A		5_prime_UTR_variant	2/7	ENST00000356413.5	NP_001542.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGBP1	ENST00000356413	c.-55T>A		5_prime_UTR_variant	2/7	1	NM_001551.3	ENSP00000348784.4
IGBP1	ENST00000342206	c.-55T>A		5_prime_UTR_variant	1/6	1		ENSP00000363661.5

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 14 AN: 112107 Hom.: 0 Cov.: 24 AF XY: 0.000117 AC XY: 4 AN XY: 34281

Gnomad AFR AF: 0.0000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000472

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00133

GnomAD4 exome AF: 0.0000475 AC: 47 AN: 988594 Hom.: 0 Cov.: 18 AF XY: 0.0000412 AC XY: 12 AN XY: 291000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000638

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: 0.0000492

Gnomad4 OTH exome AF: 0.000165

GnomAD4 genome AF: 0.000125 AC: 14 AN: 112107 Hom.: 0 Cov.: 24 AF XY: 0.000117 AC XY: 4 AN XY: 34281

Gnomad4 AFR AF: 0.0000324

Gnomad4 AMR AF: 0.000472

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00133

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.000140

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

IGBP1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs1057457133; hg19: chrX-69353743;