chr2-172967362-T-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_007023.4(RAPGEF4):c.922T>C(p.Cys308Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000247 in 1,611,228 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00023 ( 5 hom. )
Consequence
RAPGEF4
NM_007023.4 missense
NM_007023.4 missense
Scores
3
16
Clinical Significance
Conservation
PhyloP100: 3.44
Genes affected
RAPGEF4 (HGNC:16626): (Rap guanine nucleotide exchange factor 4) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in regulation of neurotransmitter receptor localization to postsynaptic specialization membrane and regulation of postsynapse organization. Predicted to act upstream of or within adenylate cyclase-activating G protein-coupled receptor signaling pathway; regulation of exocytosis; and secretion by cell. Predicted to be located in plasma membrane. Predicted to be active in glutamatergic synapse; hippocampal mossy fiber to CA3 synapse; and postsynaptic density. Implicated in autistic disorder. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006311983).
BP6
?
Variant 2-172967362-T-C is Benign according to our data. Variant chr2-172967362-T-C is described in ClinVar as [Benign]. Clinvar id is 719070.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 57 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAPGEF4 | NM_007023.4 | c.922T>C | p.Cys308Arg | missense_variant | 10/31 | ENST00000397081.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAPGEF4 | ENST00000397081.8 | c.922T>C | p.Cys308Arg | missense_variant | 10/31 | 1 | NM_007023.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000377 AC: 57AN: 151332Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000772 AC: 192AN: 248684Hom.: 2 AF XY: 0.000763 AC XY: 103AN XY: 134948
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GnomAD4 exome AF: 0.000235 AC: 343AN: 1459778Hom.: 5 Cov.: 31 AF XY: 0.000231 AC XY: 168AN XY: 726196
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GnomAD4 genome ? AF: 0.000363 AC: 55AN: 151450Hom.: 0 Cov.: 32 AF XY: 0.000487 AC XY: 36AN XY: 73980
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 25, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.;.;.;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
B;B;B;.;.;.
Vest4
MVP
MPC
ClinPred
T
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