7-1470849-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001080453.3(INTS1):āc.6454C>Gā(p.Gln2152Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,433,772 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0 ( 0 hom., cov: 33)
Exomes š: 0.000019 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
INTS1
NM_001080453.3 missense
NM_001080453.3 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 8.08
Genes affected
INTS1 (HGNC:24555): (integrator complex subunit 1) INTS1 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INTS1 | NM_001080453.3 | c.6454C>G | p.Gln2152Glu | missense_variant | 47/48 | ENST00000404767.8 | |
INTS1 | XM_011515260.2 | c.6484C>G | p.Gln2162Glu | missense_variant | 47/48 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INTS1 | ENST00000404767.8 | c.6454C>G | p.Gln2152Glu | missense_variant | 47/48 | 5 | NM_001080453.3 | P1 | |
INTS1 | ENST00000493446.1 | n.438C>G | non_coding_transcript_exon_variant | 5/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152116Hom.: 0 Cov.: 33 FAILED QC
GnomAD3 genomes
AF:
AC:
0
AN:
152116
Hom.:
Cov.:
33
FAILED QC
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000244 AC: 5AN: 205152Hom.: 0 AF XY: 0.0000269 AC XY: 3AN XY: 111588
GnomAD3 exomes
AF:
AC:
5
AN:
205152
Hom.:
AF XY:
AC XY:
3
AN XY:
111588
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000188 AC: 27AN: 1433772Hom.: 0 Cov.: 30 AF XY: 0.0000211 AC XY: 15AN XY: 711072
GnomAD4 exome
AF:
AC:
27
AN:
1433772
Hom.:
Cov.:
30
AF XY:
AC XY:
15
AN XY:
711072
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152116Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74312
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
152116
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74312
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ExAC
AF:
AC:
2
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 30, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.2629);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at