X-70133893-T-C

Variant names:

• chrX-70133893-T-C
• rs1057457133
• NM_001551.3:c.-55T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370192.1(IGBP1):​c.-50-5T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000101 in 988,594 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000010 (0 hom. 0 hem.)
• Consequence: IGBP1 NM_001370192.1 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370192.1. 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.-55T>C		5_prime_UTR	Exon 2 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.-50-5T>C		splice_region intron	N/A	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.1-55T>C		intron	N/A	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.-55T>C		5_prime_UTR	Exon 2 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.-55T>C		5_prime_UTR	Exon 1 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937167.1		c.-55T>C		5_prime_UTR	Exon 2 of 7	ENSP00000607226.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000101 AC: 1 AN: 988594 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 291000

African (AFR) AF: 0.00 AC: 0 AN: 23969

American (AMR) AF: 0.00 AC: 0 AN: 31331

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18384

East Asian (EAS) AF: 0.00 AC: 0 AN: 28527

South Asian (SAS) AF: 0.00 AC: 0 AN: 49786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3907

European-Non Finnish (NFE) AF: 0.00000133 AC: 1 AN: 751363

Other (OTH) AF: 0.00 AC: 0 AN: 42423

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		-0.43
PromoterAI		0.023	Neutral

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: rs1057457133; hg19: chrX-69353743;