7-1471181-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001080453.3(INTS1):c.6299G>A(p.Arg2100His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000657 in 1,584,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000069 ( 0 hom. )
Consequence
INTS1
NM_001080453.3 missense
NM_001080453.3 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 7.51
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.822
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
INTS1 | NM_001080453.3 | c.6299G>A | p.Arg2100His | missense_variant | 46/48 | ENST00000404767.8 | |
INTS1 | XM_011515260.2 | c.6329G>A | p.Arg2110His | missense_variant | 46/48 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
INTS1 | ENST00000404767.8 | c.6299G>A | p.Arg2100His | missense_variant | 46/48 | 5 | NM_001080453.3 | P1 | |
INTS1 | ENST00000483196.1 | c.338G>A | p.Arg113His | missense_variant | 4/4 | 5 | |||
INTS1 | ENST00000479671.1 | n.235G>A | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
INTS1 | ENST00000493446.1 | n.283G>A | non_coding_transcript_exon_variant | 4/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 34
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GnomAD4 exome AF: 0.0000691 AC: 99AN: 1431794Hom.: 0 Cov.: 31 AF XY: 0.0000719 AC XY: 51AN XY: 709244
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152206Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74354
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 20, 2024 | The c.6299G>A (p.R2100H) alteration is located in exon 46 (coding exon 45) of the INTS1 gene. This alteration results from a G to A substitution at nucleotide position 6299, causing the arginine (R) at amino acid position 2100 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;.
Polyphen
D;.
Vest4
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at