Variant 2-9418691-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004763.5(ITGB1BP1):c.7C>T(p.Arg3Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,774 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ITGB1BP1
NM_004763.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.53

Variant links:

Genes affected

ITGB1BP1 (HGNC:23927): (integrin subunit beta 1 binding protein 1) The cytoplasmic domains of integrins are essential for cell adhesion. The protein encoded by this gene binds to the beta1 integrin cytoplasmic domain. The interaction between this protein and beta1 integrin is highly specific. Two isoforms of this protein are derived from alternatively spliced transcripts. The shorter form of this protein does not interact with the beta1 integrin cytoplasmic domain. The longer form is a phosphoprotein and the extent of its phosphorylation is regulated by the cell-matrix interaction, suggesting an important role of this protein during integrin-dependent cell adhesion. Several transcript variants, some protein-coding and some non-protein coding, have been found for this gene. [provided by RefSeq, Jan 2016]

ITGB1BP1 links:

ITGB1BP1 (HGNC:):

ITGB1BP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB1BP1	NM_004763.5 linkuse as main transcript	c.7C>T	p.Arg3Cys	missense_variant	2/7	ENST00000355346.9	NP_004754.1	O14713-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB1BP1	ENST00000355346.9 linkuse as main transcript	c.7C>T	p.Arg3Cys	missense_variant	2/7	1	NM_004763.5	ENSP00000347504.4		O14713-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251476

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

show subpopulations

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 SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000540

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.7C>T (p.R3C) alteration is located in exon 2 (coding exon 1) of the ITGB1BP1 gene. This alteration results from a C to T substitution at nucleotide position 7, causing the arginine (R) at amino acid position 3 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

D;.;D;T;.;T;.;T;T;T;T;T

Eigen

Uncertain

0.63

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

.;.;D;.;D;D;D;D;D;D;D;D

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.68

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.97

L;L;L;.;L;.;.;.;.;.;.;.

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.4

N;D;N;D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;.;.;.

Polyphen

1.0

D;D;D;D;D;D;.;.;.;.;.;.

Vest4

0.80

MutPred

0.59

Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);Gain of catalytic residue at M1 (P = 5e-04);

MVP

0.53

MPC

0.47

ClinPred

0.70

GERP RS

5.5

Varity_R

0.57

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 41

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over