Genetic Variant ITGBL1:p.Gly210Arg (chr13-101579328-G-C) – 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.628G>C(p.Gly210Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52

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, 0.912

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ITGBL1	NM_004791.3 link	c.628G>C	p.Gly210Arg	missense_variant	Exon 5 of 11	ENST00000376180.8	NP_004782.1	O95965-1A0A024RDW7
ITGBL1	NM_001271755.2 link	c.481G>C	p.Gly161Arg	missense_variant	Exon 4 of 10		NP_001258684.1	O95965A0A087WY35
ITGBL1	NM_001271756.2 link	c.349G>C	p.Gly117Arg	missense_variant	Exon 4 of 10		NP_001258685.1	O95965-3
ITGBL1	NM_001271754.2 link	c.205G>C	p.Gly69Arg	missense_variant	Exon 4 of 11		NP_001258683.1	O95965-2B4DN32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ITGBL1	ENST00000376180.8 link	c.628G>C	p.Gly210Arg	missense_variant	Exon 5 of 11	1	NM_004791.3	ENSP00000365351.3	O95965-1
ITGBL1	ENST00000618057.4 link	c.481G>C	p.Gly161Arg	missense_variant	Exon 4 of 10	1		ENSP00000481484.1	A0A087WY35
ITGBL1	ENST00000376162.7 link	c.349G>C	p.Gly117Arg	missense_variant	Exon 4 of 10	2		ENSP00000365332.3	O95965-3
ITGBL1	ENST00000545560.6 link	c.205G>C	p.Gly69Arg	missense_variant	Exon 4 of 11	2		ENSP00000439903.1	O95965-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461614

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33460

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39680

South Asian (SAS)

AF:

0.00

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111828

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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

Apr 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.628G>C (p.G210R) alteration is located in exon 5 (coding exon 5) of the ITGBL1 gene. This alteration results from a G to C substitution at nucleotide position 628, causing the glycine (G) at amino acid position 210 to be replaced by an arginine (R). 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

Uncertain

0.56

BayesDel_addAF

Pathogenic

0.43

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.32

T;T;T;.;.

Eigen

Pathogenic

0.93

Eigen_PC

Pathogenic

0.89

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Pathogenic

0.52

MetaRNN

Pathogenic

0.91

D;D;D;D;D

MetaSVM

Pathogenic

1.1

MutationAssessor

Uncertain

2.5

.;M;.;.;.

PhyloP100

9.5

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-5.0

.;D;.;D;D

REVEL

Pathogenic

0.92

Sift

Uncertain

0.0010

.;D;.;D;D

Sift4G

Uncertain

0.0080

D;D;D;D;D

Polyphen

1.0

.;D;.;.;.

Vest4

0.88

MutPred

0.68

.;Gain of catalytic residue at K208 (P = 0);.;.;.;

MVP

0.89

MPC

0.86

ClinPred

1.0

GERP RS

5.3

Varity_R

0.72

gMVP

0.75

Mutation Taster

=15/85

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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13-101579328-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over