rs144371182
Positions:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM2BP4_ModerateBP6_Very_StrongBS1
The NM_021930.6(RINT1):āc.2176T>Cā(p.Tyr726His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000938 in 1,588,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00057 ( 0 hom., cov: 33)
Exomes š: 0.000043 ( 0 hom. )
Consequence
RINT1
NM_021930.6 missense
NM_021930.6 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 7.93
Genes affected
RINT1 (HGNC:21876): (RAD50 interactor 1) This gene encodes a protein first identified for its ability to interact with the RAD50 double strand break repair protein, with the resulting interaction implicated in the regulation of cell cycle progression and telomere length. The encoded protein may also play a role in trafficking of cellular cargo from the endosome to the trans-Golgi network. Mutations in this gene may be associated with breast cancer in human patients. [provided by RefSeq, Oct 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15140712).
BP6
Variant 7-105565638-T-C is Benign according to our data. Variant chr7-105565638-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 416403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000571 (87/152330) while in subpopulation AFR AF= 0.00209 (87/41586). AF 95% confidence interval is 0.00174. There are 0 homozygotes in gnomad4. There are 45 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RINT1 | NM_021930.6 | c.2176T>C | p.Tyr726His | missense_variant | 14/15 | ENST00000257700.7 | |
EFCAB10 | NM_001355526.2 | c.*-191A>G | intron_variant | ENST00000480514.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RINT1 | ENST00000257700.7 | c.2176T>C | p.Tyr726His | missense_variant | 14/15 | 1 | NM_021930.6 | P1 | |
EFCAB10 | ENST00000480514.6 | c.*-191A>G | intron_variant | 1 | NM_001355526.2 | A2 |
Frequencies
GnomAD3 genomes AF: 0.000572 AC: 87AN: 152212Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000112 AC: 28AN: 249290Hom.: 0 AF XY: 0.0000815 AC XY: 11AN XY: 134894
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GnomAD4 exome AF: 0.0000432 AC: 62AN: 1436382Hom.: 0 Cov.: 26 AF XY: 0.0000405 AC XY: 29AN XY: 716132
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GnomAD4 genome AF: 0.000571 AC: 87AN: 152330Hom.: 0 Cov.: 33 AF XY: 0.000604 AC XY: 45AN XY: 74496
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 26, 2020 | 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
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