Genetic Variant ITGBL1:p.Cys89Tyr (chr13-101454050-G-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_004791.3(ITGBL1):c.266G>A(p.Cys89Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21

Publications

0 publications found

Variant links:

Genes affected

ITGBL1 (HGNC:6164): (integrin subunit beta like 1) This gene encodes a beta integrin-related protein that is a member of the EGF-like protein family. The encoded protein contains integrin-like cysteine-rich repeats. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

ITGBL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.933

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3 link	c.266G>A	p.Cys89Tyr	missense_variant	Exon 2 of 11	ENST00000376180.8	NP_004782.1	O95965-1A0A024RDW7
ITGBL1	NM_001271755.2 link	c.266G>A	p.Cys89Tyr	missense_variant	Exon 2 of 10		NP_001258684.1	O95965A0A087WY35
ITGBL1	NM_001271754.2 link	c.-108+1119G>A		intron_variant	Intron 1 of 10		NP_001258683.1	O95965-2B4DN32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGBL1	ENST00000376180.8 link	c.266G>A	p.Cys89Tyr	missense_variant	Exon 2 of 11	1	NM_004791.3	ENSP00000365351.3	O95965-1
ITGBL1	ENST00000618057.4 link	c.266G>A	p.Cys89Tyr	missense_variant	Exon 2 of 10	1		ENSP00000481484.1	A0A087WY35
ITGBL1	ENST00000545560.6 link	c.-108+1119G>A		intron_variant	Intron 1 of 10	2		ENSP00000439903.1	O95965-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1441636

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715172

African (AFR)

AF:

0.00

AC:

AN:

32950

American (AMR)

AF:

0.00

AC:

AN:

42032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25642

East Asian (EAS)

AF:

0.00

AC:

AN:

38692

South Asian (SAS)

AF:

0.00

AC:

AN:

82150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102686

Other (OTH)

AF:

0.00

AC:

AN:

59610

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.266G>A (p.C89Y) alteration is located in exon 2 (coding exon 2) of the ITGBL1 gene. This alteration results from a G to A substitution at nucleotide position 266, causing the cysteine (C) at amino acid position 89 to be replaced by a tyrosine (Y). 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

0.99

BayesDel_addAF

Pathogenic

0.56

BayesDel_noAF

Pathogenic

0.56

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

T;T

Eigen

Pathogenic

0.96

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.72

T;D

M_CAP

Pathogenic

0.78

MetaRNN

Pathogenic

0.93

D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Pathogenic

4.1

.;H

PhyloP100

9.2

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.9

.;D

REVEL

Pathogenic

0.96

Sift

Pathogenic

0.0

.;D

Sift4G

Benign

0.13

T;D

Polyphen

1.0

.;D

Vest4

0.94

MutPred

0.71

Gain of catalytic residue at F84 (P = 0);Gain of catalytic residue at F84 (P = 0);

MVP

0.80

MPC

1.0

ClinPred

1.0

GERP RS

5.0

Varity_R

0.78

gMVP

0.96

Mutation Taster

=33/67

disease causing

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over