rs781658534

Variant names:

• chrX-70148782-C-T
• rs781658534
• NM_001551.3:c.700C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_001551.3(IGBP1):​c.700C>T​(p.Arg234Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000459 in 1,089,586 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R234L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000046 (0 hom. 1 hem.)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• 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-AS2 (HGNC:40294): (IGBP1 antisense RNA 2)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11245504).
• BS2: High AC in GnomAdExome4 at 5 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.700C>T	p.Arg234Cys	missense	Exon 5 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.700C>T	p.Arg234Cys	missense	Exon 5 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.700C>T	p.Arg234Cys	missense	Exon 5 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.700C>T	p.Arg234Cys	missense	Exon 5 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.700C>T	p.Arg234Cys	missense	Exon 4 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.700C>T	p.Arg234Cys	missense	Exon 5 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.0000331 AC: 6 AN: 181238 AF XY: 0.0000456

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000435

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000459 AC: 5 AN: 1089586 Hom.: 0 Cov.: 27 AF XY: 0.00000281 AC XY: 1 AN XY: 355542

African (AFR) AF: 0.00 AC: 0 AN: 26241

American (AMR) AF: 0.00 AC: 0 AN: 35183

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19320

East Asian (EAS) AF: 0.000166 AC: 5 AN: 30167

South Asian (SAS) AF: 0.00 AC: 0 AN: 53701

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4109

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 834588

Other (OTH) AF: 0.00 AC: 0 AN: 45791

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.077
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.088	T
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.18	T
M_CAP	Pathogenic	0.30	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.5
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.088
Sift	Benign	0.080	T
Sift4G	Benign	0.089	T
Polyphen		0.017	B
Vest4		0.16
MutPred		0.38		Loss of solvent accessibility (P = 0.0561)
MVP		0.41
MPC		0.60
ClinPred		0.23	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.17
gMVP		0.44
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs781658534; hg19: chrX-69368632;