11-119345521-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_031433.4(MFRP):c.540T>C(p.His180His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 1,613,992 control chromosomes in the GnomAD database, including 725,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.92 ( 64584 hom., cov: 32)

Exomes 𝑓: 0.95 ( 660865 hom. )

Consequence

MFRP
NM_031433.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.25

Publications

31 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]

MFRP links:

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

C1QTNF5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 11-119345521-A-G is Benign according to our data. Variant chr11-119345521-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 167297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4 link	c.540T>C	p.His180His	synonymous_variant	Exon 5 of 15	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5 link	c.-2097T>C		5_prime_UTR_variant	Exon 5 of 15		NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6 link	c.540T>C	p.His180His	synonymous_variant	Exon 5 of 15	1	NM_031433.4	ENSP00000481824.1

Frequencies

GnomAD3 genomes

AF:

0.920

AC:

139959

AN:

152098

Hom.:

64526

Cov.:

show subpopulations

Gnomad AFR

AF:

0.870

Gnomad AMI

AF:

0.996

Gnomad AMR

AF:

0.867

Gnomad ASJ

AF:

0.913

Gnomad EAS

AF:

0.862

Gnomad SAS

AF:

0.964

Gnomad FIN

AF:

0.938

Gnomad MID

AF:

0.946

Gnomad NFE

AF:

0.960

Gnomad OTH

AF:

0.917

GnomAD2 exomes

AF:

0.932

AC:

231719

AN:

248740

AF XY:

0.938

show subpopulations

Gnomad AFR exome

AF:

0.873

Gnomad AMR exome

AF:

0.859

Gnomad ASJ exome

AF:

0.918

Gnomad EAS exome

AF:

0.870

Gnomad FIN exome

AF:

0.938

Gnomad NFE exome

AF:

0.962

Gnomad OTH exome

AF:

0.932

GnomAD4 exome

AF:

0.950

AC:

1389338

AN:

1461776

Hom.:

660865

Cov.:

AF XY:

0.952

AC XY:

692158

AN XY:

727184

show subpopulations

African (AFR)

AF:

0.864

AC:

28911

AN:

33480

American (AMR)

AF:

0.862

AC:

38536

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.917

AC:

23979

AN:

26136

East Asian (EAS)

AF:

0.873

AC:

34645

AN:

39700

South Asian (SAS)

AF:

0.971

AC:

83716

AN:

86258

European-Finnish (FIN)

AF:

0.940

AC:

50140

AN:

53328

Middle Eastern (MID)

AF:

0.946

AC:

5457

AN:

5768

European-Non Finnish (NFE)

AF:

0.960

AC:

1067114

AN:

1111992

Other (OTH)

AF:

0.941

AC:

56840

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

4569

9138

13708

18277

22846

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21620

43240

64860

86480

108100

<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:

0.920

AC:

140073

AN:

152216

Hom.:

64584

Cov.:

AF XY:

0.919

AC XY:

68413

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.871

AC:

36159

AN:

41522

American (AMR)

AF:

0.866

AC:

13253

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.913

AC:

3169

AN:

3472

East Asian (EAS)

AF:

0.862

AC:

4440

AN:

5150

South Asian (SAS)

AF:

0.964

AC:

4657

AN:

4832

European-Finnish (FIN)

AF:

0.938

AC:

9955

AN:

10616

Middle Eastern (MID)

AF:

0.949

AC:

279

AN:

294

European-Non Finnish (NFE)

AF:

0.960

AC:

65323

AN:

68012

Other (OTH)

AF:

0.915

AC:

1930

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

566

1132

1698

2264

2830

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

908

1816

2724

3632

4540

<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:

0.942

Hom.:

145870

Bravo

AF:

0.911

Asia WGS

AF:

0.917

AC:

3191

AN:

3478

EpiCase

AF:

0.959

EpiControl

AF:

0.959

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 24, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Isolated microphthalmia 6

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal degeneration

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Isolated microphthalmia 5

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.31

(source)

DANN

Benign

0.59

PhyloP100

-2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over