X-70134657-A-G

Variant names:

• chrX-70134657-A-G
• rs148273635
• NM_001551.3:c.323A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001551.3(IGBP1):​c.323A>G​(p.His108Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,210,559 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000080 (0 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.000014 (0 hom. 0 hem.)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.29
• 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 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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.39489657).
• BS2: High AC in GnomAd4 at 9 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.323A>G	p.His108Arg	missense	Exon 3 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.323A>G	p.His108Arg	missense	Exon 3 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.323A>G	p.His108Arg	missense	Exon 3 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.323A>G	p.His108Arg	missense	Exon 3 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.323A>G	p.His108Arg	missense	Exon 2 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.323A>G	p.His108Arg	missense	Exon 3 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes AF: 0.0000801 AC: 9 AN: 112408 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000291

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: 0.00

GnomAD2 exomes AF: 0.0000218 AC: 4 AN: 183494 AF XY: 0.00

Gnomad AFR exome AF: 0.000304

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000137 AC: 15 AN: 1098151 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363507

African (AFR) AF: 0.000492 AC: 13 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54144

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842048

Other (OTH) AF: 0.0000434 AC: 2 AN: 46093

GnomAD4 genome AF: 0.0000801 AC: 9 AN: 112408 Hom.: 0 Cov.: 23 AF XY: 0.000116 AC XY: 4 AN XY: 34564

African (AFR) AF: 0.000291 AC: 9 AN: 30929

American (AMR) AF: 0.00 AC: 0 AN: 10622

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3564

South Asian (SAS) AF: 0.00 AC: 0 AN: 2737

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53316

Other (OTH) AF: 0.00 AC: 0 AN: 1506

Alfa AF: 0.000147 Hom.: 0

Bravo AF: 0.0000907

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		6.3
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.046	D
Polyphen		0.93	P
Vest4		0.48
MVP		0.77
MPC		1.2
ClinPred		0.92	D
GERP RS		4.9
Varity_R		0.79
gMVP		0.73
Mutation Taster		=30/70	disease causing

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: rs148273635; hg19: chrX-69354507;