Variant 17-75752027-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000213.5(ITGB4):c.3794-147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 855,400 control chromosomes in the GnomAD database, including 77,571 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.37 ( 11480 hom., cov: 32)

Exomes 𝑓: 0.43 ( 66091 hom. )

Consequence

ITGB4
NM_000213.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.68

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 17-75752027-C-T is Benign according to our data. Variant chr17-75752027-C-T is described in ClinVar as [Benign]. Clinvar id is 1287294.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 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.3794-147C>T		intron_variant		ENST00000200181.8	NP_000204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ITGB4	ENST00000200181.8 linkuse as main transcript	c.3794-147C>T		intron_variant		1	NM_000213.5	ENSP00000200181		P16144-1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55897

AN:

151934

Hom.:

11477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.172

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.438

Gnomad ASJ

AF:

0.350

Gnomad EAS

AF:

0.471

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.449

Gnomad MID

AF:

0.364

Gnomad NFE

AF:

0.446

Gnomad OTH

AF:

0.384

GnomAD4 exome

AF:

0.429

AC:

301581

AN:

703348

Hom.:

66091

AF XY:

0.430

AC XY:

162419

AN XY:

377802

show subpopulations

Gnomad4 AFR exome

AF:

0.172

Gnomad4 AMR exome

AF:

0.444

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.430

Gnomad4 FIN exome

AF:

0.447

Gnomad4 NFE exome

AF:

0.441

Gnomad4 OTH exome

AF:

0.411

GnomAD4 genome

AF:

0.368

AC:

55919

AN:

152052

Hom.:

11480

Cov.:

AF XY:

0.372

AC XY:

27662

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.437

Gnomad4 ASJ

AF:

0.350

Gnomad4 EAS

AF:

0.470

Gnomad4 SAS

AF:

0.440

Gnomad4 FIN

AF:

0.449

Gnomad4 NFE

AF:

0.446

Gnomad4 OTH

AF:

0.388

Alfa

AF:

0.417

Hom.:

3338

Bravo

AF:

0.355

Asia WGS

AF:

0.447

AC:

1557

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.036

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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