X-70146758-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001551.3(IGBP1):​c.608T>C​(p.Ile203Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00558 in 1,172,798 control chromosomes in the GnomAD database, including 11 homozygotes. There are 1,952 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 Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0035 (4 hom., 98 hem., cov: 22)
  • Exomes 𝑓: 0.0058 (7 hom. 1854 hem.)
• Consequence: IGBP1 NM_001551.3 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010424465).
• BP6: Variant X-70146758-T-C is Benign according to our data. Variant chrX-70146758-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 499182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 382 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.608T>C	p.Ile203Thr	missense	Exon 4 of 7	NP_001542.1	P78318
	IGBP1	NM_001370192.1		c.608T>C	p.Ile203Thr	missense	Exon 4 of 7	NP_001357121.1	P78318
	IGBP1	NM_001370193.1		c.608T>C	p.Ile203Thr	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>C	p.Ile203Thr	missense	Exon 4 of 7	ENSP00000348784.4	P78318
	IGBP1	ENST00000342206.10	TSL:1	c.608T>C	p.Ile203Thr	missense	Exon 3 of 6	ENSP00000363661.5	P78318
	IGBP1	ENST00000937166.1		c.608T>C	p.Ile203Thr	missense	Exon 4 of 7	ENSP00000607225.1

Frequencies

GnomAD3 genomes AF: 0.00345 AC: 381 AN: 110490 Hom.: 4 Cov.: 22

Gnomad AFR AF: 0.000626

Gnomad AMI AF: 0.00146

Gnomad AMR AF: 0.00126

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00524

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00596

Gnomad OTH AF: 0.00134

GnomAD2 exomes AF: 0.00361 AC: 641 AN: 177726 AF XY: 0.00370

Gnomad AFR exome AF: 0.000508

Gnomad AMR exome AF: 0.000808

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00552

Gnomad NFE exome AF: 0.00635

Gnomad OTH exome AF: 0.00406

GnomAD4 exome AF: 0.00580 AC: 6163 AN: 1062253 Hom.: 7 Cov.: 29 AF XY: 0.00549 AC XY: 1854 AN XY: 337517

African (AFR) AF: 0.00164 AC: 40 AN: 24401

American (AMR) AF: 0.000941 AC: 33 AN: 35061

Ashkenazi Jewish (ASJ) AF: 0.000210 AC: 4 AN: 19063

East Asian (EAS) AF: 0.0000335 AC: 1 AN: 29881

South Asian (SAS) AF: 0.000529 AC: 28 AN: 52943

European-Finnish (FIN) AF: 0.00621 AC: 251 AN: 40413

Middle Eastern (MID) AF: 0.000247 AC: 1 AN: 4054

European-Non Finnish (NFE) AF: 0.00693 AC: 5627 AN: 811642

Other (OTH) AF: 0.00397 AC: 178 AN: 44795

GnomAD4 genome AF: 0.00346 AC: 382 AN: 110545 Hom.: 4 Cov.: 22 AF XY: 0.00299 AC XY: 98 AN XY: 32779

African (AFR) AF: 0.000625 AC: 19 AN: 30401

American (AMR) AF: 0.00126 AC: 13 AN: 10322

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3487

South Asian (SAS) AF: 0.000387 AC: 1 AN: 2583

European-Finnish (FIN) AF: 0.00524 AC: 30 AN: 5724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 215

European-Non Finnish (NFE) AF: 0.00596 AC: 316 AN: 52980

Other (OTH) AF: 0.00132 AC: 2 AN: 1514

Alfa AF: 0.00148 Hom.: 14

Bravo AF: 0.00306

TwinsUK AF: 0.00701 AC: 26

ALSPAC AF: 0.00658 AC: 19

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00654 AC: 44

ExAC AF: 0.0179 AC: 2171

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.80
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.5
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.055
Sift	Benign	0.41	T
Sift4G	Benign	0.61	T
Polyphen		0.0010	B
Vest4		0.078
MPC		0.55
ClinPred		0.0031	T
GERP RS		4.0
Varity_R		0.064
gMVP		0.26
Mutation Taster		=92/8	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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; COSMIC: COSV60555678; COSMIC: COSV60555678;