11-119345794-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_015645.5(C1QTNF5):c.-2231G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,613,314 control chromosomes in the GnomAD database, including 78,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.25 ( 5540 hom., cov: 32)
Exomes 𝑓: 0.31 ( 73308 hom. )
Consequence
C1QTNF5
NM_015645.5 5_prime_UTR_premature_start_codon_gain
NM_015645.5 5_prime_UTR_premature_start_codon_gain
Scores
18
Clinical Significance
Conservation
PhyloP100: -2.46
Genes affected
MFRP (HGNC:18121): (membrane frizzled-related protein) This gene encodes a member of the frizzled-related protein family. The encoded protein plays an important role in eye development and mutations in this gene have been associated with nanophthalmos, posterior microphthalmia, retinitis pigmentosa, foveoschisis, and optic disc drusen. The protein is encoded by a bicistronic transcript which also encodes C1q and tumor necrosis factor related protein 5 (C1QTNF5). [provided by RefSeq, Jun 2013]
C1QTNF5 (HGNC:14344): (C1q and TNF related 5) This gene encodes a member of a family of proteins that function as components of basement membranes and may play a role in cell adhesion. Mutations in this gene have been associated with late-onset retinal degeneration. The protein may be encoded by either a bicistronic transcript including sequence from the upstream membrane frizzled-related protein gene (MFRP), or by a monocistronic transcript expressed from an internal promoter. [provided by RefSeq, Jun 2013]
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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=0.004874885).
BP6
Variant 11-119345794-C-T is Benign according to our data. Variant chr11-119345794-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 167299.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119345794-C-T is described in Lovd as [Benign]. Variant chr11-119345794-C-T is described in Lovd as [Likely_benign].
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MFRP | NM_031433.4 | c.406G>A | p.Val136Met | missense_variant | 4/15 | ENST00000619721.6 | NP_113621.1 | |
C1QTNF5 | NM_015645.5 | c.-2231G>A | 5_prime_UTR_premature_start_codon_gain_variant | 4/15 | NP_056460.1 | |||
C1QTNF5 | NM_015645.5 | c.-2231G>A | 5_prime_UTR_variant | 4/15 | NP_056460.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.246 AC: 37345AN: 151884Hom.: 5541 Cov.: 32
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GnomAD3 exomes AF: 0.265 AC: 65587AN: 247454Hom.: 9618 AF XY: 0.273 AC XY: 36616AN XY: 134096
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GnomAD4 exome AF: 0.311 AC: 454796AN: 1461312Hom.: 73308 Cov.: 65 AF XY: 0.311 AC XY: 225727AN XY: 726938
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GnomAD4 genome AF: 0.246 AC: 37336AN: 152002Hom.: 5540 Cov.: 32 AF XY: 0.244 AC XY: 18112AN XY: 74298
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 15, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Isolated microphthalmia 5 Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2025 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Isolated microphthalmia 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Retinal degeneration Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
.;N
REVEL
Benign
Sift
Benign
.;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
ClinPred
T
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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