chrX-70146713-G-A

Variant names:

• chrX-70146713-G-A
• rs748197652
• NM_001551.3:c.563G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001551.3(IGBP1):​c.563G>A​(p.Arg188His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000819 in 109,862 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000082 (0 hom., 2 hem., cov: 21)
  • Exomes 𝑓: 0.000021 (0 hom. 5 hem.)
  • Failed GnomAD Quality Control
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03667164).
• 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.563G>A	p.Arg188His	missense	Exon 4 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.563G>A	p.Arg188His	missense	Exon 4 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.563G>A	p.Arg188His	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.563G>A	p.Arg188His	missense	Exon 4 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.563G>A	p.Arg188His	missense	Exon 3 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.563G>A	p.Arg188His	missense	Exon 4 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes AF: 0.0000819 AC: 9 AN: 109862 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.000265

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: 0.0000383 AC: 7 AN: 182620 AF XY: 0.0000149

Gnomad AFR exome AF: 0.000231

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000724

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000368

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000213 AC: 23 AN: 1080635 Hom.: 0 Cov.: 29 AF XY: 0.0000144 AC XY: 5 AN XY: 348063

African (AFR) AF: 0.000196 AC: 5 AN: 25567

American (AMR) AF: 0.0000284 AC: 1 AN: 35162

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19249

East Asian (EAS) AF: 0.0000332 AC: 1 AN: 30103

South Asian (SAS) AF: 0.0000187 AC: 1 AN: 53584

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4085

European-Non Finnish (NFE) AF: 0.0000133 AC: 11 AN: 826896

Other (OTH) AF: 0.0000879 AC: 4 AN: 45487

GnomAD4 genome AF: 0.0000819 AC: 9 AN: 109862 Hom.: 0 Cov.: 21 AF XY: 0.0000623 AC XY: 2 AN XY: 32098

African (AFR) AF: 0.000265 AC: 8 AN: 30204

American (AMR) AF: 0.00 AC: 0 AN: 10173

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2623

East Asian (EAS) AF: 0.00 AC: 0 AN: 3472

South Asian (SAS) AF: 0.00 AC: 0 AN: 2547

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.0000189 AC: 1 AN: 52849

Other (OTH) AF: 0.00 AC: 0 AN: 1486

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000718

ExAC AF: 0.000642 AC: 78

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	0.062
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.2
DANN	Benign	0.78
DEOGEN2	Benign	0.019	T
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.078
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.047
Sift	Benign	0.56	T
Sift4G	Benign	0.55	T
Polyphen		0.011	B
Vest4		0.12
MVP		0.39
MPC		0.54
ClinPred		0.0075	T
GERP RS		-3.4
Varity_R		0.089
gMVP		0.21
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs748197652; hg19: chrX-69366563; COSMIC: COSV60555670; COSMIC: COSV60555670;