Variant 13-101567827-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004791.3(ITGBL1):c.445A>T(p.Ile149Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,613,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.411

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06900972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ITGBL1	NM_004791.3 linkuse as main transcript	c.445A>T	p.Ile149Phe	missense_variant	3/11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271756.2 linkuse as main transcript	c.166A>T	p.Ile56Phe	missense_variant	2/10		NP_001258685.1
ITGBL1	NM_001271754.2 linkuse as main transcript	c.22A>T	p.Ile8Phe	missense_variant	2/11		NP_001258683.1
ITGBL1	NM_001271755.2 linkuse as main transcript	c.317-7597A>T		intron_variant			NP_001258684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8 linkuse as main transcript	c.445A>T	p.Ile149Phe	missense_variant	3/11	1	NM_004791.3	ENSP00000365351	P1	O95965-1
ITGBL1	ENST00000618057.4 linkuse as main transcript	c.317-7597A>T		intron_variant		1		ENSP00000481484
ITGBL1	ENST00000376162.7 linkuse as main transcript	c.166A>T	p.Ile56Phe	missense_variant	2/10	2		ENSP00000365332		O95965-3
ITGBL1	ENST00000545560.6 linkuse as main transcript	c.22A>T	p.Ile8Phe	missense_variant	2/11	2		ENSP00000439903		O95965-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

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:

0.0000439

AC:

AN:

250792

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135528

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.0000580

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:

0.0000353

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1460882

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

726754

show subpopulations

Gnomad4 AFR exome

AF:

0.0000898

Gnomad4 AMR exome

AF:

0.0000896

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:

0.0000189

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000105

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000328

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:

0.0000282

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Mar 31, 2023

The c.445A>T (p.I149F) alteration is located in exon 3 (coding exon 3) of the ITGBL1 gene. This alteration results from a A to T substitution at nucleotide position 445, causing the isoleucine (I) at amino acid position 149 to be replaced by a phenylalanine (F). 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

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.018

T;T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.82

T;D;T;T

M_CAP

Uncertain

0.085

MetaRNN

Benign

0.069

T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.1

M;.;.;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.23

N;.;N;N

REVEL

Benign

0.21

Sift

Benign

0.061

T;.;D;D

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.025

B;.;.;.

Vest4

0.29

MVP

0.26

MPC

0.32

ClinPred

0.032

GERP RS

-5.2

Varity_R

0.061

gMVP

0.64

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