rs763753687

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000889.3(ITGB7):​c.2158G>T​(p.Gly720*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

ITGB7
NM_000889.3 stop_gained, splice_region

Scores

2
1
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.560

Publications

0 publications found
Variant links:
Genes affected
ITGB7 (HGNC:6162): (integrin subunit beta 7) This gene encodes a protein that is a member of the integrin superfamily. Members of this family are adhesion receptors that function in signaling from the extracellular matrix to the cell. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. The encoded protein forms dimers with an alpha4 chain or an alphaE chain and plays a role in leukocyte adhesion. Dimerization with alpha4 forms a homing receptor for migration of lymphocytes to the intestinal mucosa and Peyer's patches. Dimerization with alphaE permits binding to the ligand epithelial cadherin, a calcium-dependent adhesion molecule. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Sep 2013]
ZNF740 (HGNC:27465): (zinc finger protein 740) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITGB7NM_000889.3 linkc.2158G>T p.Gly720* stop_gained, splice_region_variant Exon 15 of 16 ENST00000267082.10 NP_000880.1 P26010-1
ZNF740NM_001004304.4 linkc.*4427C>A 3_prime_UTR_variant Exon 7 of 7 ENST00000416904.5 NP_001004304.1 Q8NDX6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITGB7ENST00000267082.10 linkc.2158G>T p.Gly720* stop_gained, splice_region_variant Exon 15 of 16 1 NM_000889.3 ENSP00000267082.4 P26010-1
ZNF740ENST00000416904.5 linkc.*4427C>A 3_prime_UTR_variant Exon 7 of 7 1 NM_001004304.4 ENSP00000409463.2 Q8NDX6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1458432
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
725200
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33346
American (AMR)
AF:
0.00
AC:
0
AN:
44392
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26026
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39636
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86192
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
52734
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5756
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110152
Other (OTH)
AF:
0.00
AC:
0
AN:
60198
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.38
D
BayesDel_noAF
Pathogenic
0.30
CADD
Pathogenic
36
DANN
Benign
0.97
Eigen
Uncertain
0.29
Eigen_PC
Benign
-0.024
FATHMM_MKL
Benign
0.25
N
PhyloP100
0.56
Vest4
0.13
GERP RS
2.9
PromoterAI
-0.0057
Neutral
Mutation Taster
=21/179
disease causing (fs/PTC)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs763753687; hg19: chr12-53585801; API