NM_000213.5:c.80-36G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

epidermolysis bullosa simplex
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
junctional epidermolysis bullosa with pyloric atresia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics, Genomics England PanelApp
junctional epidermolysis bullosa, non-Herlitz type
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
aplasia cutis congenita
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
epidermolysis bullosa simplex 5C, with pyloric atresia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
generalized junctional epidermolysis bullosa non-Herlitz type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
localized junctional epidermolysis bullosa, non-Herlitz type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
epidermolysis bullosa simplex 1C, localized
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ITGB4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000213.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGB4	NM_000213.5	MANE Select	c.80-36G>A	intron	N/A	NP_000204.3
ITGB4	NM_001005619.2		c.80-36G>A	intron	N/A	NP_001005619.1
ITGB4	NM_001005731.3		c.80-36G>A	intron	N/A	NP_001005731.1	P16144-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ITGB4	ENST00000200181.8	TSL:1 MANE Select	c.80-36G>A	intron	N/A	ENSP00000200181.3	P16144-1
ITGB4	ENST00000449880.7	TSL:1	c.80-36G>A	intron	N/A	ENSP00000400217.2	P16144-3
ITGB4	ENST00000450894.7	TSL:1	c.80-36G>A	intron	N/A	ENSP00000405536.3	P16144-2

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

GnomAD2 exomes

AF:

0.508

AC:

123440

AN:

243170

AF XY:

0.518

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 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

African (AFR)

AF:

0.129

AC:

4232

AN:

32772

American (AMR)

AF:

0.462

AC:

20393

AN:

44126

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

10801

AN:

25906

East Asian (EAS)

AF:

0.432

AC:

16880

AN:

39112

South Asian (SAS)

AF:

0.514

AC:

43743

AN:

85106

European-Finnish (FIN)

AF:

0.562

AC:

29879

AN:

53140

Middle Eastern (MID)

AF:

0.466

AC:

2662

AN:

5710

European-Non Finnish (NFE)

AF:

0.584

AC:

637960

AN:

1091882

Other (OTH)

AF:

0.525

AC:

31216

AN:

59510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

18469

36938

55408

73877

92346

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17256

34512

51768

69024

86280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.442

AC:

67181

AN:

152028

Hom.:

17517

Cov.:

AF XY:

0.444

AC XY:

33009

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.148

AC:

6158

AN:

41488

American (AMR)

AF:

0.493

AC:

7529

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

1478

AN:

3470

East Asian (EAS)

AF:

0.471

AC:

2437

AN:

5174

South Asian (SAS)

AF:

0.517

AC:

2492

AN:

4818

European-Finnish (FIN)

AF:

0.566

AC:

5974

AN:

10554

Middle Eastern (MID)

AF:

0.517

AC:

152

AN:

294

European-Non Finnish (NFE)

AF:

0.580

AC:

39375

AN:

67930

Other (OTH)

AF:

0.454

AC:

956

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1660

3320

4979

6639

8299

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

608

1216

1824

2432

3040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.533

Hom.:

83697

Bravo

AF:

0.418

Asia WGS

AF:

0.497

AC:

1729

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.65

(source)

DANN

Benign

0.46

PhyloP100

-0.92

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over