chrX-70133962-C-T

Variant names:

• chrX-70133962-C-T
• rs147789194
• NM_001551.3:c.15C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001551.3(IGBP1):​c.15C>T​(p.Asp5Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,209,254 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 56 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00070 (0 hom., 26 hem., cov: 23)
  • Exomes 𝑓: 0.000098 (0 hom. 30 hem.)
• Consequence: IGBP1 NM_001551.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.720
• 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 Gene-Disease associations (from GenCC):

• corpus callosum agenesis-intellectual disability-coloboma-micrognathia syndrome

  Inheritance: XL, Unknown, AD Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant X-70133962-C-T is Benign according to our data. Variant chrX-70133962-C-T is described in ClinVar as Benign. ClinVar VariationId is 709966.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.72 with no splicing effect.
• BS2: High AC in GnomAd4 at 78 XL,Unknown,AD gene.

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.15C>T	p.Asp5Asp	synonymous	Exon 2 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.15C>T	p.Asp5Asp	synonymous	Exon 2 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.15C>T	p.Asp5Asp	synonymous	Exon 2 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.15C>T	p.Asp5Asp	synonymous	Exon 2 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.15C>T	p.Asp5Asp	synonymous	Exon 1 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.15C>T	p.Asp5Asp	synonymous	Exon 2 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes AF: 0.000695 AC: 78 AN: 112177 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00246

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00133

GnomAD2 exomes AF: 0.000265 AC: 48 AN: 181443 AF XY: 0.000242

Gnomad AFR exome AF: 0.00332

Gnomad AMR exome AF: 0.000147

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: 0.000224

GnomAD4 exome AF: 0.0000984 AC: 108 AN: 1097025 Hom.: 0 Cov.: 30 AF XY: 0.0000828 AC XY: 30 AN XY: 362435

African (AFR) AF: 0.00353 AC: 93 AN: 26379

American (AMR) AF: 0.000114 AC: 4 AN: 35173

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19376

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.00 AC: 0 AN: 54060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40488

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 841183

Other (OTH) AF: 0.000217 AC: 10 AN: 46047

GnomAD4 genome AF: 0.000695 AC: 78 AN: 112229 Hom.: 0 Cov.: 23 AF XY: 0.000755 AC XY: 26 AN XY: 34439

African (AFR) AF: 0.00246 AC: 76 AN: 30911

American (AMR) AF: 0.00 AC: 0 AN: 10637

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3543

South Asian (SAS) AF: 0.00 AC: 0 AN: 2714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6116

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53231

Other (OTH) AF: 0.00131 AC: 2 AN: 1523

Alfa AF: 0.00121 Hom.: 3

Bravo AF: 0.000888

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.7
DANN	Benign	0.91
PhyloP100		-0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs147789194; hg19: chrX-69353812;