17-75757580-C-T

Variant names:

• chr17-75757580-C-T
• rs9367
• NM_000213.5:c.*25C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.843
• Publications: 28 publications found

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]

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 Gene-Disease associations (from GenCC):

• galactokinase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Myriad Women’s Health, Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ITGB4	NM_000213.5	c.*25C>T		3_prime_UTR_variant	Exon 40 of 40	ENST00000200181.8	NP_000204.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ITGB4	ENST00000200181.8	c.*25C>T		3_prime_UTR_variant	Exon 40 of 40	1	NM_000213.5	ENSP00000200181.3

Frequencies

GnomAD3 genomes AF: 0.715 AC: 108485 AN: 151800 Hom.: 39912 Cov.: 31

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

GnomAD2 exomes AF: 0.744 AC: 186477 AN: 250492 AF XY: 0.744

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 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.: 52 AF XY: 0.781 AC XY: 567479 AN XY: 726718

African (AFR) AF: 0.520 AC: 17415 AN: 33468

American (AMR) AF: 0.803 AC: 35887 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 19415 AN: 26130

East Asian (EAS) AF: 0.592 AC: 23481 AN: 39688

South Asian (SAS) AF: 0.674 AC: 58128 AN: 86250

European-Finnish (FIN) AF: 0.806 AC: 42468 AN: 52722

Middle Eastern (MID) AF: 0.712 AC: 4101 AN: 5758

European-Non Finnish (NFE) AF: 0.807 AC: 897658 AN: 1111752

Other (OTH) AF: 0.768 AC: 46341 AN: 60364

GnomAD4 genome AF: 0.714 AC: 108529 AN: 151918 Hom.: 39922 Cov.: 31 AF XY: 0.717 AC XY: 53250 AN XY: 74246

African (AFR) AF: 0.537 AC: 22239 AN: 41406

American (AMR) AF: 0.792 AC: 12100 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.755 AC: 2618 AN: 3468

East Asian (EAS) AF: 0.565 AC: 2902 AN: 5138

South Asian (SAS) AF: 0.694 AC: 3340 AN: 4814

European-Finnish (FIN) AF: 0.797 AC: 8425 AN: 10568

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54516 AN: 67942

Other (OTH) AF: 0.730 AC: 1540 AN: 2110

Alfa AF: 0.773 Hom.: 46271

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Junctional epidermolysis bullosa with pyloric atresia Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Junctional epidermolysis bullosa, non-Herlitz type Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Epidermolysis bullosa simplex 1C, localized Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Deficiency of galactokinase Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.47
DANN	Benign	0.48
PhyloP100		-0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=4/96	disease causing

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

Other links and lift over

dbSNP: rs9367; hg19: chr17-73753661; COSMIC: COSV52326951; COSMIC: COSV52326951;