11-119344061-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_031433.4(MFRP):​c.976-97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,498,876 control chromosomes in the GnomAD database, including 248,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 19797 hom., cov: 29)
Exomes 𝑓: 0.58 ( 228462 hom. )

Consequence

MFRP
NM_031433.4 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.06

Publications

9 publications found
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]
C1QTNF5 Gene-Disease associations (from GenCC):
  • late-onset retinal degeneration
    Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 11-119344061-A-G is Benign according to our data. Variant chr11-119344061-A-G is described in ClinVar as [Benign]. Clinvar id is 1229543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MFRPNM_031433.4 linkc.976-97T>C intron_variant Intron 8 of 14 ENST00000619721.6 NP_113621.1 Q9BY79-1
C1QTNF5NM_015645.5 linkc.-1661-97T>C intron_variant Intron 8 of 14 NP_056460.1 Q9BXJ0A0A024R3F8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MFRPENST00000619721.6 linkc.976-97T>C intron_variant Intron 8 of 14 1 NM_031433.4 ENSP00000481824.1 Q9BY79-1
MFRPENST00000360167.4 linkc.898+571T>C intron_variant Intron 7 of 9 2 ENSP00000353291.4 Q9BY79-2

Frequencies

GnomAD3 genomes
AF:
0.490
AC:
74083
AN:
151212
Hom.:
19808
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.267
Gnomad AMI
AF:
0.498
Gnomad AMR
AF:
0.570
Gnomad ASJ
AF:
0.468
Gnomad EAS
AF:
0.302
Gnomad SAS
AF:
0.642
Gnomad FIN
AF:
0.625
Gnomad MID
AF:
0.487
Gnomad NFE
AF:
0.590
Gnomad OTH
AF:
0.504
GnomAD4 exome
AF:
0.577
AC:
777904
AN:
1347544
Hom.:
228462
AF XY:
0.579
AC XY:
390923
AN XY:
674898
show subpopulations
African (AFR)
AF:
0.243
AC:
7646
AN:
31506
American (AMR)
AF:
0.611
AC:
25944
AN:
42436
Ashkenazi Jewish (ASJ)
AF:
0.462
AC:
11653
AN:
25234
East Asian (EAS)
AF:
0.333
AC:
12948
AN:
38930
South Asian (SAS)
AF:
0.628
AC:
51964
AN:
82720
European-Finnish (FIN)
AF:
0.611
AC:
24967
AN:
40888
Middle Eastern (MID)
AF:
0.485
AC:
2515
AN:
5188
European-Non Finnish (NFE)
AF:
0.595
AC:
609155
AN:
1023836
Other (OTH)
AF:
0.548
AC:
31112
AN:
56806
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
17307
34614
51920
69227
86534
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
16056
32112
48168
64224
80280
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.489
AC:
74070
AN:
151332
Hom.:
19797
Cov.:
29
AF XY:
0.495
AC XY:
36553
AN XY:
73910
show subpopulations
African (AFR)
AF:
0.267
AC:
10964
AN:
41126
American (AMR)
AF:
0.570
AC:
8678
AN:
15228
Ashkenazi Jewish (ASJ)
AF:
0.468
AC:
1619
AN:
3462
East Asian (EAS)
AF:
0.301
AC:
1532
AN:
5090
South Asian (SAS)
AF:
0.641
AC:
3067
AN:
4786
European-Finnish (FIN)
AF:
0.625
AC:
6552
AN:
10486
Middle Eastern (MID)
AF:
0.493
AC:
145
AN:
294
European-Non Finnish (NFE)
AF:
0.590
AC:
40011
AN:
67854
Other (OTH)
AF:
0.500
AC:
1050
AN:
2098
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.506
Heterozygous variant carriers
0
1748
3496
5243
6991
8739
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
658
1316
1974
2632
3290
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.553
Hom.:
34251
Bravo
AF:
0.469

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:not provided

- -

Nov 12, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
3.7
DANN
Benign
0.39
PhyloP100
-2.1
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs948413; hg19: chr11-119214771; COSMIC: COSV107466106; COSMIC: COSV107466106; API