rs13277
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001366722.1(GRIP1):āc.2461C>Gā(p.Gln821Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.972 in 1,587,370 control chromosomes in the GnomAD database, including 755,875 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.88 ( 61226 hom., cov: 32)
Exomes š: 0.98 ( 694649 hom. )
Consequence
GRIP1
NM_001366722.1 missense
NM_001366722.1 missense
Scores
1
3
12
Clinical Significance
Conservation
PhyloP100: 7.63
Genes affected
GRIP1 (HGNC:18708): (glutamate receptor interacting protein 1) This gene encodes a member of the glutamate receptor interacting protein family. The encoded scaffold protein binds to and mediates the trafficking and membrane organization of a number of transmembrane proteins. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, May 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=8.574098E-7).
BP6
?
Variant 12-66392311-G-C is Benign according to our data. Variant chr12-66392311-G-C is described in ClinVar as [Benign]. Clinvar id is 261410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-66392311-G-C is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIP1 | NM_001366722.1 | c.2461C>G | p.Gln821Glu | missense_variant | 19/25 | ENST00000359742.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIP1 | ENST00000359742.9 | c.2461C>G | p.Gln821Glu | missense_variant | 19/25 | 5 | NM_001366722.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.883 AC: 134343AN: 152090Hom.: 61211 Cov.: 32
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GnomAD3 exomes AF: 0.951 AC: 237058AN: 249228Hom.: 114010 AF XY: 0.962 AC XY: 130121AN XY: 135230
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GnomAD4 exome AF: 0.982 AC: 1409044AN: 1435162Hom.: 694649 Cov.: 26 AF XY: 0.984 AC XY: 704320AN XY: 715744
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GnomAD4 genome ? AF: 0.883 AC: 134402AN: 152208Hom.: 61226 Cov.: 32 AF XY: 0.885 AC XY: 65872AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Fraser syndrome 1 Benign:3
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | Oct 09, 2014 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 25, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Fraser syndrome 3 Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T;T
Sift4G
Benign
T;T;.;T;.
Polyphen
P;P;P;.;.
Vest4
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