Variant chr13-101579386-G-A 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.686G>A(p.Arg229Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,613,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

ITGBL1
NM_004791.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

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=0.11208567).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ITGBL1	NM_004791.3 linkuse as main transcript	c.686G>A	p.Arg229Gln	missense_variant	5/11	ENST00000376180.8	NP_004782.1
ITGBL1	NM_001271755.2 linkuse as main transcript	c.539G>A	p.Arg180Gln	missense_variant	4/10		NP_001258684.1
ITGBL1	NM_001271756.2 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	4/10		NP_001258685.1
ITGBL1	NM_001271754.2 linkuse as main transcript	c.263G>A	p.Arg88Gln	missense_variant	4/11		NP_001258683.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGBL1	ENST00000376180.8 linkuse as main transcript	c.686G>A	p.Arg229Gln	missense_variant	5/11	1	NM_004791.3	ENSP00000365351	P1	O95965-1
ITGBL1	ENST00000618057.4 linkuse as main transcript	c.539G>A	p.Arg180Gln	missense_variant	4/10	1		ENSP00000481484
ITGBL1	ENST00000376162.7 linkuse as main transcript	c.407G>A	p.Arg136Gln	missense_variant	4/10	2		ENSP00000365332		O95965-3
ITGBL1	ENST00000545560.6 linkuse as main transcript	c.263G>A	p.Arg88Gln	missense_variant	4/11	2		ENSP00000439903		O95965-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251090

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135710

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000527

AC:

AN:

1461554

Hom.:

Cov.:

AF XY:

0.0000633

AC XY:

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

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:

0.0000639

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000169

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000247

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

Jun 16, 2024

The c.686G>A (p.R229Q) alteration is located in exon 5 (coding exon 5) of the ITGBL1 gene. This alteration results from a G to A substitution at nucleotide position 686, causing the arginine (R) at amino acid position 229 to be replaced by a glutamine (Q). 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

0.064

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.14

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0074

T;T;T;.;.

Eigen

Benign

-0.079

Eigen_PC

Benign

0.060

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.89

D;D;D;D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Uncertain

-0.047

MutationAssessor

Benign

0.55

.;N;.;.;.

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.15

.;N;.;N;N

REVEL

Benign

0.26

Sift

Benign

0.36

.;T;.;T;T

Sift4G

Benign

0.30

T;T;T;T;T

Polyphen

0.18

.;B;.;.;.

Vest4

0.32

MutPred

0.36

.;Gain of catalytic residue at S233 (P = 0.0015);.;.;.;

MVP

0.58

MPC

0.23

ClinPred

0.12

GERP RS

4.6

Varity_R

0.038

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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