11-119345794-C-T

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

Scores

18

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.46
Variant links:
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]

Genome browser will be placed here

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
MFRPNM_031433.4 linkc.406G>A p.Val136Met missense_variant 4/15 ENST00000619721.6 NP_113621.1 Q9BY79-1
C1QTNF5NM_015645.5 linkc.-2231G>A 5_prime_UTR_premature_start_codon_gain_variant 4/15 NP_056460.1 Q9BXJ0A0A024R3F8
C1QTNF5NM_015645.5 linkc.-2231G>A 5_prime_UTR_variant 4/15 NP_056460.1 Q9BXJ0A0A024R3F8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MFRPENST00000619721.6 linkc.406G>A p.Val136Met missense_variant 4/151 NM_031433.4 ENSP00000481824.1 Q9BY79-1

Frequencies

GnomAD3 genomes
AF:
0.246
AC:
37345
AN:
151884
Hom.:
5541
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0890
Gnomad AMI
AF:
0.502
Gnomad AMR
AF:
0.221
Gnomad ASJ
AF:
0.310
Gnomad EAS
AF:
0.195
Gnomad SAS
AF:
0.214
Gnomad FIN
AF:
0.324
Gnomad MID
AF:
0.370
Gnomad NFE
AF:
0.332
Gnomad OTH
AF:
0.291
GnomAD3 exomes
AF:
0.265
AC:
65587
AN:
247454
Hom.:
9618
AF XY:
0.273
AC XY:
36616
AN XY:
134096
show subpopulations
Gnomad AFR exome
AF:
0.0855
Gnomad AMR exome
AF:
0.164
Gnomad ASJ exome
AF:
0.303
Gnomad EAS exome
AF:
0.198
Gnomad SAS exome
AF:
0.223
Gnomad FIN exome
AF:
0.311
Gnomad NFE exome
AF:
0.332
Gnomad OTH exome
AF:
0.288
GnomAD4 exome
AF:
0.311
AC:
454796
AN:
1461312
Hom.:
73308
Cov.:
65
AF XY:
0.311
AC XY:
225727
AN XY:
726938
show subpopulations
Gnomad4 AFR exome
AF:
0.0799
Gnomad4 AMR exome
AF:
0.174
Gnomad4 ASJ exome
AF:
0.307
Gnomad4 EAS exome
AF:
0.205
Gnomad4 SAS exome
AF:
0.230
Gnomad4 FIN exome
AF:
0.316
Gnomad4 NFE exome
AF:
0.334
Gnomad4 OTH exome
AF:
0.303
GnomAD4 genome
AF:
0.246
AC:
37336
AN:
152002
Hom.:
5540
Cov.:
32
AF XY:
0.244
AC XY:
18112
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.0890
Gnomad4 AMR
AF:
0.220
Gnomad4 ASJ
AF:
0.310
Gnomad4 EAS
AF:
0.195
Gnomad4 SAS
AF:
0.215
Gnomad4 FIN
AF:
0.324
Gnomad4 NFE
AF:
0.332
Gnomad4 OTH
AF:
0.289
Alfa
AF:
0.311
Hom.:
11239
Bravo
AF:
0.233
TwinsUK
AF:
0.345
AC:
1280
ALSPAC
AF:
0.331
AC:
1276
ESP6500AA
AF:
0.0975
AC:
429
ESP6500EA
AF:
0.323
AC:
2771
ExAC
AF:
0.265
AC:
32153
Asia WGS
AF:
0.189
AC:
657
AN:
3478
EpiCase
AF:
0.340
EpiControl
AF:
0.338

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 submitterclinical testingEurofins Ntd Llc (ga)Oct 15, 2015- -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Isolated microphthalmia 5 Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 03, 2025- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Isolated microphthalmia 6 Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Retinal degeneration Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.71
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
0.011
DANN
Benign
0.86
DEOGEN2
Benign
0.025
T;.
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.0024
N
LIST_S2
Benign
0.57
T;T
MetaRNN
Benign
0.0049
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
-1.1
N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.0
.;N
REVEL
Benign
0.039
Sift
Benign
1.0
.;T
Sift4G
Benign
0.64
T;T
Polyphen
0.0080
B;.
Vest4
0.047
ClinPred
0.00030
T
GERP RS
-3.1
Varity_R
0.023
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3814762; hg19: chr11-119216504; COSMIC: COSV64128333; COSMIC: COSV64128333; API