Variant chr17-75727159-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000213.5(ITGB4):c.80-36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,589,292 control chromosomes in the GnomAD database, including 243,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 17517 hom., cov: 32)

Exomes 𝑓: 0.56 ( 226203 hom. )

Consequence

ITGB4
NM_000213.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.918

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:

ITGB4 (HGNC:):

ITGB4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-75727159-G-A is Benign according to our data. Variant chr17-75727159-G-A is described in ClinVar as [Benign]. Clinvar id is 1229138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.575 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.80-36G>A		intron_variant		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.80-36G>A		intron_variant		1	NM_000213.5	ENSP00000200181.3		P16144-1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67159

AN:

151910

Hom.:

17511

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.694

Gnomad AMR

AF:

0.493

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.517

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.528

Gnomad NFE

AF:

0.580

Gnomad OTH

AF:

0.447

GnomAD3 exomes

AF:

0.508

AC:

123440

AN:

243170

Hom.:

32726

AF XY:

0.518

AC XY:

68130

AN XY:

131536

show subpopulations

Gnomad AFR exome

AF:

0.134

Gnomad AMR exome

AF:

0.465

Gnomad ASJ exome

AF:

0.415

Gnomad EAS exome

AF:

0.484

Gnomad SAS exome

AF:

0.509

Gnomad FIN exome

AF:

0.561

Gnomad NFE exome

AF:

0.575

Gnomad OTH exome

AF:

0.517

GnomAD4 exome

AF:

0.555

AC:

797766

AN:

1437264

Hom.:

226203

Cov.:

AF XY:

0.555

AC XY:

397163

AN XY:

716088

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.462

Gnomad4 ASJ exome

AF:

0.417

Gnomad4 EAS exome

AF:

0.432

Gnomad4 SAS exome

AF:

0.514

Gnomad4 FIN exome

AF:

0.562

Gnomad4 NFE exome

AF:

0.584

Gnomad4 OTH exome

AF:

0.525

GnomAD4 genome

AF:

0.442

AC:

67181

AN:

152028

Hom.:

17517

Cov.:

AF XY:

0.444

AC XY:

33009

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.148

Gnomad4 AMR

AF:

0.493

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.517

Gnomad4 FIN

AF:

0.566

Gnomad4 NFE

AF:

0.580

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.549

Hom.:

38221

Bravo

AF:

0.418

Asia WGS

AF:

0.497

AC:

1729

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.65

DANN

Benign

0.46

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