13-42888292-T-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000313640.11(EPSTI1):​c.1191A>G​(p.Ile397Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000081 in 1,604,908 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I397T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00037 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 2 hom. )

Consequence

EPSTI1
ENST00000313640.11 missense

Scores

15

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.238

Publications

0 publications found
Variant links:
Genes affected
EPSTI1 (HGNC:16465): (epithelial stromal interaction 1) The protein encoded by this gene has been shown to promote tumor invasion and metastasis in some invasive cancer cells when overexpressed. Expression of this gene has been shown to be upregulated by direct binding of the Kruppel like factor 8 protein to promoter sequences. The translated protein interacts with the amino terminal region of the valosin containing protein gene product, resulting in the nuclear translocation of the nuclear factor kappa B subunit 1 gene product, and activation of target genes. Overexpression of this gene has been observed in some breast cancers and in some individuals with systemic lupus erythematosus (SLE). [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.0064947903).
BP6
Variant 13-42888292-T-C is Benign according to our data. Variant chr13-42888292-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2277615.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EPSTI1NM_033255.5 linkc.*202A>G 3_prime_UTR_variant Exon 11 of 11 ENST00000313624.12 NP_150280.1 Q96J88-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EPSTI1ENST00000313640.11 linkc.1191A>G p.Ile397Met missense_variant Exon 13 of 13 1 ENSP00000318982.7 Q96J88-3
EPSTI1ENST00000313624.12 linkc.*202A>G 3_prime_UTR_variant Exon 11 of 11 1 NM_033255.5 ENSP00000318643.7 Q96J88-2
EPSTI1ENST00000540470.5 linkn.2699A>G non_coding_transcript_exon_variant Exon 11 of 11 2
EPSTI1ENST00000398762.7 linkc.*202A>G downstream_gene_variant 5 ENSP00000381746.3 Q96J88-1

Frequencies

GnomAD3 genomes
AF:
0.000374
AC:
56
AN:
149588
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000252
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00351
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000485
GnomAD2 exomes
AF:
0.000180
AC:
45
AN:
249780
AF XY:
0.000148
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00131
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000509
AC:
74
AN:
1455224
Hom.:
2
Cov.:
33
AF XY:
0.0000428
AC XY:
31
AN XY:
723648
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32302
American (AMR)
AF:
0.00155
AC:
68
AN:
43868
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25934
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39340
South Asian (SAS)
AF:
0.00
AC:
0
AN:
84574
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53300
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5746
European-Non Finnish (NFE)
AF:
0.00000450
AC:
5
AN:
1110108
Other (OTH)
AF:
0.0000167
AC:
1
AN:
60052
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.496
Heterozygous variant carriers
0
4
8
12
16
20
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
2
4
6
8
10
<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:
0.000374
AC:
56
AN:
149684
Hom.:
1
Cov.:
32
AF XY:
0.000465
AC XY:
34
AN XY:
73140
show subpopulations
African (AFR)
AF:
0.0000251
AC:
1
AN:
39790
American (AMR)
AF:
0.00350
AC:
53
AN:
15124
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3434
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5000
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4672
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10514
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
292
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
67868
Other (OTH)
AF:
0.000481
AC:
1
AN:
2080
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.512
Heterozygous variant carriers
0
3
6
9
12
15
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.000336
ExAC
AF:
0.0000741
AC:
9

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Jul 20, 2021
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.61
T
BayesDel_noAF
Benign
-0.68
CADD
Benign
5.8
DANN
Benign
0.11
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.028
N
LIST_S2
Benign
0.23
T
M_CAP
Benign
0.0062
T
MetaRNN
Benign
0.0065
T
MetaSVM
Benign
-0.98
T
PhyloP100
-0.24
PrimateAI
Benign
0.27
T
PROVEAN
Benign
0.22
N
REVEL
Benign
0.024
Sift
Benign
0.32
T
Polyphen
0.0020
B
Vest4
0.11
MutPred
0.30
Gain of helix (P = 0.1736);
MVP
0.12
MPC
0.11
ClinPred
0.020
T
GERP RS
-1.4
gMVP
0.064
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs751190720; hg19: chr13-43462428; API