Genetic Variant IGBP1:c.-55T>A (chrX-70133893-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001370192.1(IGBP1):c.-50-5T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,100,701 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.000048 ( 0 hom. 12 hem. )

Consequence

IGBP1
NM_001370192.1 splice_region, intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.429

Publications

1 publications found

Variant links:

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

IGBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant X-70133893-T-A is Benign according to our data. Variant chrX-70133893-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2660802.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 14 XL,Unknown,AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370192.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGBP1	NM_001551.3	MANE Select	c.-55T>A	5_prime_UTR	Exon 2 of 7	NP_001542.1	P78318
IGBP1	NM_001370192.1		c.-50-5T>A	splice_region intron	N/A	NP_001357121.1	P78318
IGBP1	NM_001370193.1		c.1-55T>A	intron	N/A	NP_001357122.1	P78318

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IGBP1	ENST00000356413.5	TSL:1 MANE Select	c.-55T>A	5_prime_UTR	Exon 2 of 7	ENSP00000348784.4	P78318
IGBP1	ENST00000342206.10	TSL:1	c.-55T>A	5_prime_UTR	Exon 1 of 6	ENSP00000363661.5	P78318
IGBP1	ENST00000937167.1		c.-55T>A	5_prime_UTR	Exon 2 of 7	ENSP00000607226.1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

112107

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000472

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:

0.000113

Gnomad OTH

AF:

0.00133

GnomAD4 exome

AF:

0.0000475

AC:

AN:

988594

Hom.:

Cov.:

AF XY:

0.0000412

AC XY:

AN XY:

291000

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23969

American (AMR)

AF:

0.0000638

AC:

AN:

31331

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18384

East Asian (EAS)

AF:

0.00

AC:

AN:

28527

South Asian (SAS)

AF:

0.00

AC:

AN:

49786

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38904

Middle Eastern (MID)

AF:

0.000256

AC:

AN:

3907

European-Non Finnish (NFE)

AF:

0.0000492

AC:

AN:

751363

Other (OTH)

AF:

0.000165

AC:

AN:

42423

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000125

AC:

AN:

112107

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34281

show subpopulations

African (AFR)

AF:

0.0000324

AC:

AN:

30852

American (AMR)

AF:

0.000472

AC:

AN:

10603

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2650

East Asian (EAS)

AF:

0.00

AC:

AN:

3566

South Asian (SAS)

AF:

0.00

AC:

AN:

2702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53206

Other (OTH)

AF:

0.00133

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000140

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.2

(source)

DANN

Benign

0.50

PhyloP100

-0.43

PromoterAI

-0.049

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over