Variant 13-101575497-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004791.3(ITGBL1):c.537G>T(p.Glu179Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,612,614 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: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.408

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:

Genome browser will be placed here

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
ITGBL1	NM_004791.3 linkuse as main transcript	c.537G>T	p.Glu179Asp	missense_variant	4/11	ENST00000376180.8	NP_004782.1	O95965-1A0A024RDW7
ITGBL1	NM_001271755.2 linkuse as main transcript	c.390G>T	p.Glu130Asp	missense_variant	3/10		NP_001258684.1	O95965A0A087WY35
ITGBL1	NM_001271756.2 linkuse as main transcript	c.258G>T	p.Glu86Asp	missense_variant	3/10		NP_001258685.1	O95965-3
ITGBL1	NM_001271754.2 linkuse as main transcript	c.114G>T	p.Glu38Asp	missense_variant	3/11		NP_001258683.1	O95965-2B4DN32

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ITGBL1	ENST00000376180.8 linkuse as main transcript	c.537G>T	p.Glu179Asp	missense_variant	4/11	1	NM_004791.3	ENSP00000365351.3	O95965-1
ITGBL1	ENST00000618057.4 linkuse as main transcript	c.390G>T	p.Glu130Asp	missense_variant	3/10	1		ENSP00000481484.1	A0A087WY35
ITGBL1	ENST00000376162.7 linkuse as main transcript	c.258G>T	p.Glu86Asp	missense_variant	3/10	2		ENSP00000365332.3	O95965-3
ITGBL1	ENST00000545560.6 linkuse as main transcript	c.114G>T	p.Glu38Asp	missense_variant	3/11	2		ENSP00000439903.1	O95965-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251238

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135780

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1460496

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726648

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000567

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 11, 2024

The c.537G>T (p.E179D) alteration is located in exon 4 (coding exon 4) of the ITGBL1 gene. This alteration results from a G to T substitution at nucleotide position 537, causing the glutamic acid (E) at amino acid position 179 to be replaced by an aspartic acid (D). 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

0.66

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

T;T;T;.;.

Eigen

Benign

0.090

Eigen_PC

Benign

0.059

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.85

D;D;D;D;D

M_CAP

Uncertain

0.15

MetaRNN

Uncertain

0.46

T;T;T;T;T

MetaSVM

Uncertain

0.77

MutationAssessor

Uncertain

2.7

.;M;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.47

.;N;.;N;N

REVEL

Uncertain

0.54

Sift

Benign

0.068

.;T;.;D;D

Sift4G

Uncertain

0.058

T;T;T;T;T

Polyphen

1.0

.;D;.;.;.

Vest4

0.62

MutPred

0.37

.;Gain of catalytic residue at K176 (P = 0.0082);.;.;.;

MVP

0.69

MPC

0.72

ClinPred

0.60

GERP RS

1.5

Varity_R

0.10

gMVP

0.59

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

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