17-75727159-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.918

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
ITGB4	NM_000213.5	c.80-36G>A		intron_variant		ENST00000200181.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ITGB4	ENST00000200181.8	c.80-36G>A		intron_variant		1	NM_000213.5

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67159 AN: 151910 Hom.: 17511 Cov.: 32

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

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.: 27 AF XY: 0.555 AC XY: 397163 AN XY: 716088

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.: 32 AF XY: 0.444 AC XY: 33009 AN XY: 74318

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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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

Other links and lift over

dbSNP: rs2584100; hg19: chr17-73723239;