17-75757580-C-T

Position:

chr17-75757580-C-T

Variant summary

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

The NM_000213.5(ITGB4):c.*25C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 1,612,750 control chromosomes in the GnomAD database, including 491,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.71 ( 39922 hom., cov: 31)

Exomes 𝑓: 0.78 ( 452015 hom. )

Consequence

ITGB4
NM_000213.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.843

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:

GALK1 (HGNC:):

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 (BayesDel_noAF=-0.87).

BP6

Variant 17-75757580-C-T is Benign according to our data. Variant chr17-75757580-C-T is described in ClinVar as [Benign]. Clinvar id is 325219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ITGB4	NM_000213.5 linkuse as main transcript	c.*25C>T		3_prime_UTR_variant	40/40	ENST00000200181.8	NP_000204.3	P16144-1A0A024R8T0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB4	ENST00000200181.8 linkuse as main transcript	c.*25C>T		3_prime_UTR_variant	40/40	1	NM_000213.5	ENSP00000200181.3		P16144-1

Frequencies

GnomAD3 genomes

AF:

0.715

AC:

108485

AN:

151800

Hom.:

39912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.538

Gnomad AMI

AF:

0.709

Gnomad AMR

AF:

0.792

Gnomad ASJ

AF:

0.755

Gnomad EAS

AF:

0.564

Gnomad SAS

AF:

0.695

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.693

Gnomad NFE

AF:

0.802

Gnomad OTH

AF:

0.735

GnomAD3 exomes

AF:

0.744

AC:

186477

AN:

250492

Hom.:

70467

AF XY:

0.744

AC XY:

100996

AN XY:

135688

show subpopulations

Gnomad AFR exome

AF:

0.530

Gnomad AMR exome

AF:

0.802

Gnomad ASJ exome

AF:

0.739

Gnomad EAS exome

AF:

0.567

Gnomad SAS exome

AF:

0.669

Gnomad FIN exome

AF:

0.799

Gnomad NFE exome

AF:

0.796

Gnomad OTH exome

AF:

0.772

GnomAD4 exome

AF:

0.784

AC:

1144894

AN:

1460832

Hom.:

452015

Cov.:

AF XY:

0.781

AC XY:

567479

AN XY:

726718

show subpopulations

Gnomad4 AFR exome

AF:

0.520

Gnomad4 AMR exome

AF:

0.803

Gnomad4 ASJ exome

AF:

0.743

Gnomad4 EAS exome

AF:

0.592

Gnomad4 SAS exome

AF:

0.674

Gnomad4 FIN exome

AF:

0.806

Gnomad4 NFE exome

AF:

0.807

Gnomad4 OTH exome

AF:

0.768

GnomAD4 genome

AF:

0.714

AC:

108529

AN:

151918

Hom.:

39922

Cov.:

AF XY:

0.717

AC XY:

53250

AN XY:

74246

show subpopulations

Gnomad4 AFR

AF:

0.537

Gnomad4 AMR

AF:

0.792

Gnomad4 ASJ

AF:

0.755

Gnomad4 EAS

AF:

0.565

Gnomad4 SAS

AF:

0.694

Gnomad4 FIN

AF:

0.797

Gnomad4 NFE

AF:

0.802

Gnomad4 OTH

AF:

0.730

Alfa

AF:

0.774

Hom.:

34355

Bravo

AF:

0.704

Asia WGS

AF:

0.644

AC:

2236

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Junctional epidermolysis bullosa with pyloric atresia

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 19, 2021	- -

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

-0.87

CADD

Benign

0.47

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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