X-70146758-T-G

Variant names:

• chrX-70146758-T-G
• rs61755732
• NM_001551.3:c.608T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001551.3(IGBP1):​c.608T>G​(p.Ile203Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000905 in 110,492 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. 13/21 in silico tools predict a benign outcome for this variant. 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. I203T) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000091 (0 hom., 0 hem., cov: 22)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49
• Publications: 3 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.355604).

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.608T>G	p.Ile203Ser	missense	Exon 4 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.608T>G	p.Ile203Ser	missense	Exon 4 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.608T>G	p.Ile203Ser	missense	Exon 4 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.608T>G	p.Ile203Ser	missense	Exon 4 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.608T>G	p.Ile203Ser	missense	Exon 3 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.608T>G	p.Ile203Ser	missense	Exon 4 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes AF: 0.00000905 AC: 1 AN: 110492 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

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: 0.0000189

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000563 AC: 1 AN: 177726 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 29

GnomAD4 genome AF: 0.00000905 AC: 1 AN: 110492 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32714

African (AFR) AF: 0.00 AC: 0 AN: 30334

American (AMR) AF: 0.00 AC: 0 AN: 10309

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.00 AC: 0 AN: 3497

South Asian (SAS) AF: 0.00 AC: 0 AN: 2591

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52987

Other (OTH) AF: 0.00 AC: 0 AN: 1494

Alfa AF: 0.00 Hom.: 14

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.12
Sift	Benign	0.11	T
Sift4G	Benign	0.72	T
Polyphen		0.34	B
Vest4		0.47
MutPred		0.42		Gain of disorder (P = 0.0085)
MVP		0.47
MPC		0.94
ClinPred		0.28	T
GERP RS		4.0
Varity_R		0.14
gMVP		0.52
Mutation Taster		=87/13	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: rs61755732; hg19: chrX-69366608;