chr17-75757422-T-C

Position:

chr17-75757422-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000213.5(ITGB4):c.5336T>C(p.Leu1779Pro) variant causes a missense change. The variant allele was found at a frequency of 0.748 in 1,612,904 control chromosomes in the GnomAD database, including 462,348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar.

Frequency

Genomes: 𝑓 0.63 ( 33925 hom., cov: 33)

Exomes 𝑓: 0.76 ( 428423 hom. )

Consequence

ITGB4
NM_000213.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 3.78

Variant links:

Genes affected

ITGB4 (HGNC:6158): (integrin subunit beta 4) Integrins are heterodimers comprised of alpha and beta subunits, that are noncovalently associated transmembrane glycoprotein receptors. Different combinations of alpha and beta polypeptides form complexes that vary in their ligand-binding specificities. Integrins mediate cell-matrix or cell-cell adhesion, and transduced signals that regulate gene expression and cell growth. This gene encodes the integrin beta 4 subunit, a receptor for the laminins. This subunit tends to associate with alpha 6 subunit and is likely to play a pivotal role in the biology of invasive carcinoma. Mutations in this gene are associated with epidermolysis bullosa with pyloric atresia. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ITGB4 links:

GALK1 (HGNC:4118): (galactokinase 1) Galactokinase is a major enzyme for the metabolism of galactose and its deficiency causes congenital cataracts during infancy and presenile cataracts in the adult population. [provided by RefSeq, Jul 2008]

GALK1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.72673E-6).

BP6

Variant 17-75757422-T-C is Benign according to our data. Variant chr17-75757422-T-C is described in ClinVar as [Benign]. Clinvar id is 255543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75757422-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ITGB4	NM_000213.5 linkuse as main transcript	c.5336T>C	p.Leu1779Pro	missense_variant	40/40	ENST00000200181.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB4	ENST00000200181.8 linkuse as main transcript	c.5336T>C	p.Leu1779Pro	missense_variant	40/40	1	NM_000213.5		P16144-1

Frequencies

GnomAD3 genomes

AF:

0.627

AC:

95341

AN:

151966

Hom.:

33915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.705

Gnomad AMR

AF:

0.761

Gnomad ASJ

AF:

0.681

Gnomad EAS

AF:

0.634

Gnomad SAS

AF:

0.735

Gnomad FIN

AF:

0.804

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.778

Gnomad OTH

AF:

0.663

GnomAD3 exomes

AF:

0.725

AC:

181328

AN:

250144

Hom.:

68017

AF XY:

0.730

AC XY:

98949

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.793

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.638

Gnomad SAS exome

AF:

0.723

Gnomad FIN exome

AF:

0.809

Gnomad NFE exome

AF:

0.775

Gnomad OTH exome

AF:

0.741

GnomAD4 exome

AF:

0.760

AC:

1110544

AN:

1460820

Hom.:

428423

Cov.:

AF XY:

0.759

AC XY:

551853

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.791

Gnomad4 ASJ exome

AF:

0.674

Gnomad4 EAS exome

AF:

0.643

Gnomad4 SAS exome

AF:

0.722

Gnomad4 FIN exome

AF:

0.811

Gnomad4 NFE exome

AF:

0.784

Gnomad4 OTH exome

AF:

0.733

GnomAD4 genome

AF:

0.627

AC:

95372

AN:

152084

Hom.:

33925

Cov.:

AF XY:

0.635

AC XY:

47219

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.265

Gnomad4 AMR

AF:

0.761

Gnomad4 ASJ

AF:

0.681

Gnomad4 EAS

AF:

0.634

Gnomad4 SAS

AF:

0.735

Gnomad4 FIN

AF:

0.804

Gnomad4 NFE

AF:

0.778

Gnomad4 OTH

AF:

0.661

Alfa

AF:

0.750

Hom.:

80849

Bravo

AF:

0.607

TwinsUK

AF:

0.772

AC:

2864

ALSPAC

AF:

0.786

AC:

3030

ESP6500AA

AF:

0.280

AC:

1235

ESP6500EA

AF:

0.769

AC:

6615

ExAC

AF:

0.713

AC:

86491

Asia WGS

AF:

0.665

AC:

2310

AN:

3478

EpiCase

AF:

0.760

EpiControl

AF:

0.764

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Junctional epidermolysis bullosa with pyloric atresia

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Mendelics	May 28, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 18, 2019	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Epidermolysis bullosa simplex 1C, localized

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Deficiency of galactokinase

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Benign

0.92

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.91

MetaRNN

Benign

0.0000027

T;T;T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

3.8e-16

P;P;P;P;P;P

PrimateAI

Uncertain

0.56

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.99, 1.0

.;D;.;D

Vest4

0.20

MPC

0.88

ClinPred

0.016

GERP RS

4.2

Varity_R

0.66

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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