chrX-70148800-G-C

Variant names:

• chrX-70148800-G-C
• rs376859259
• NM_001551.3:c.718G>C

Variant summary

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

The NM_001551.3(IGBP1):​c.718G>C​(p.Val240Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000829 in 1,205,857 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000082 (0 hom. 0 hem.)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.668
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06320879).
• BS2: High AC in GnomAdExome4 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.718G>C	p.Val240Leu	missense	Exon 5 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.718G>C	p.Val240Leu	missense	Exon 5 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.718G>C	p.Val240Leu	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.718G>C	p.Val240Leu	missense	Exon 5 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.718G>C	p.Val240Leu	missense	Exon 4 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.718G>C	p.Val240Leu	missense	Exon 5 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes AF: 0.00000887 AC: 1 AN: 112780 Hom.: 0 Cov.: 23

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: 0.0000187

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000549 AC: 1 AN: 182035 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: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000823 AC: 9 AN: 1093077 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 358615

African (AFR) AF: 0.00 AC: 0 AN: 26306

American (AMR) AF: 0.00 AC: 0 AN: 35191

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19336

East Asian (EAS) AF: 0.00 AC: 0 AN: 30183

South Asian (SAS) AF: 0.00 AC: 0 AN: 53869

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40505

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4123

European-Non Finnish (NFE) AF: 0.0000107 AC: 9 AN: 837626

Other (OTH) AF: 0.00 AC: 0 AN: 45938

GnomAD4 genome AF: 0.00000887 AC: 1 AN: 112780 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34928

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31055

American (AMR) AF: 0.00 AC: 0 AN: 10707

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3595

South Asian (SAS) AF: 0.00 AC: 0 AN: 2774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000187 AC: 1 AN: 53374

Other (OTH) AF: 0.00 AC: 0 AN: 1519

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000297 AC: 2

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	IGBP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.71
DEOGEN2	Benign	0.0078	T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.37	N
PhyloP100		0.67
PrimateAI	Benign	0.21	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.031
Sift	Benign	0.90	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.17
MutPred		0.53		Loss of sheet (P = 0.0228)
MVP		0.23
MPC		0.42
ClinPred		0.065	T
GERP RS		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.051
gMVP		0.33
Mutation Taster		=95/5	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: rs376859259; hg19: chrX-69368650;