17-75754778-C-G

Position:

chr17-75754778-C-G

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000213.5(ITGB4):c.4521C>G(p.Pro1507=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,613,648 control chromosomes in the GnomAD database, including 182,550 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P1507P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.39 ( 13132 hom., cov: 32)

Exomes 𝑓: 0.48 ( 169418 hom. )

Consequence

ITGB4
NM_000213.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 1.19

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 17-75754778-C-G is Benign according to our data. Variant chr17-75754778-C-G is described in ClinVar as [Benign]. Clinvar id is 255542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-75754778-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 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.4521C>G	p.Pro1507=	synonymous_variant	34/40	ENST00000200181.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB4	ENST00000200181.8 linkuse as main transcript	c.4521C>G	p.Pro1507=	synonymous_variant	34/40	1	NM_000213.5		P16144-1

Frequencies

GnomAD3 genomes

AF:

0.385

AC:

58544

AN:

151918

Hom.:

13135

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.468

Gnomad ASJ

AF:

0.369

Gnomad EAS

AF:

0.494

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.484

Gnomad MID

AF:

0.367

Gnomad NFE

AF:

0.489

Gnomad OTH

AF:

0.415

GnomAD3 exomes

AF:

0.455

AC:

114338

AN:

251118

Hom.:

27133

AF XY:

0.460

AC XY:

62505

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.130

Gnomad AMR exome

AF:

0.471

Gnomad ASJ exome

AF:

0.385

Gnomad EAS exome

AF:

0.512

Gnomad SAS exome

AF:

0.442

Gnomad FIN exome

AF:

0.481

Gnomad NFE exome

AF:

0.493

Gnomad OTH exome

AF:

0.454

GnomAD4 exome

AF:

0.477

AC:

696779

AN:

1461612

Hom.:

169418

Cov.:

AF XY:

0.476

AC XY:

346136

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.466

Gnomad4 ASJ exome

AF:

0.383

Gnomad4 EAS exome

AF:

0.460

Gnomad4 SAS exome

AF:

0.443

Gnomad4 FIN exome

AF:

0.485

Gnomad4 NFE exome

AF:

0.494

Gnomad4 OTH exome

AF:

0.451

GnomAD4 genome

AF:

0.385

AC:

58538

AN:

152036

Hom.:

13132

Cov.:

AF XY:

0.389

AC XY:

28927

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.468

Gnomad4 ASJ

AF:

0.369

Gnomad4 EAS

AF:

0.494

Gnomad4 SAS

AF:

0.447

Gnomad4 FIN

AF:

0.484

Gnomad4 NFE

AF:

0.489

Gnomad4 OTH

AF:

0.419

Alfa

AF:

0.419

Hom.:

4233

Bravo

AF:

0.372

Asia WGS

AF:

0.449

AC:

1563

AN:

3478

EpiCase

AF:

0.479

EpiControl

AF:

0.488

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Junctional epidermolysis bullosa with pyloric atresia

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

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

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.1

DANN

Benign

0.84

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