7-1470849-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001080453.3(INTS1):ā€‹c.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

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.08
Variant links:
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
INTS1NM_001080453.3 linkuse as main transcriptc.6454C>G p.Gln2152Glu missense_variant 47/48 ENST00000404767.8
INTS1XM_011515260.2 linkuse as main transcriptc.6484C>G p.Gln2162Glu missense_variant 47/48

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
INTS1ENST00000404767.8 linkuse as main transcriptc.6454C>G p.Gln2152Glu missense_variant 47/485 NM_001080453.3 P1
INTS1ENST00000493446.1 linkuse as main transcriptn.438C>G non_coding_transcript_exon_variant 5/63

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
152116
Hom.:
0
Cov.:
33
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000244
AC:
5
AN:
205152
Hom.:
0
AF XY:
0.0000269
AC XY:
3
AN XY:
111588
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000339
Gnomad SAS 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:
0.0000188
AC:
27
AN:
1433772
Hom.:
0
Cov.:
30
AF XY:
0.0000211
AC XY:
15
AN XY:
711072
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000659
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.10e-7
Gnomad4 OTH exome
AF:
0.0000168
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
152116
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74312
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000167
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 submitterclinical testingGeneDxMay 30, 2019In 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.32
T
Eigen
Uncertain
0.42
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.020
T
MetaRNN
Uncertain
0.58
D
MetaSVM
Benign
-0.61
T
MutationAssessor
Uncertain
2.1
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Benign
-2.1
N
REVEL
Uncertain
0.36
Sift
Benign
0.070
T
Sift4G
Benign
0.10
T
Polyphen
0.73
P
Vest4
0.73
MutPred
0.70
Gain of relative solvent accessibility (P = 0.2629);
MVP
0.61
ClinPred
0.27
T
GERP RS
5.6
Varity_R
0.29
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs761770199; hg19: chr7-1510485; API