rs36015759

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.492C>T(p.Tyr164Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,692 control chromosomes in the GnomAD database, including 37,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3717 hom., cov: 32)

Exomes 𝑓: 0.21 ( 33970 hom. )

Consequence

MFRP
NM_031433.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.39

Publications

24 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=-0.51).

BP6

Variant 11-119345569-G-A is Benign according to our data. Variant chr11-119345569-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 143157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.39 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4 link	c.492C>T	p.Tyr164Tyr	synonymous_variant	Exon 5 of 15	ENST00000619721.6	NP_113621.1	Q9BY79-1
C1QTNF5	NM_015645.5 link	c.-2145C>T		5_prime_UTR_variant	Exon 5 of 15		NP_056460.1	Q9BXJ0A0A024R3F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6 link	c.492C>T	p.Tyr164Tyr	synonymous_variant	Exon 5 of 15	1	NM_031433.4	ENSP00000481824.1		Q9BY79-1

Frequencies

GnomAD3 genomes

AF:

0.218

AC:

33077

AN:

151996

Hom.:

3714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.287

Gnomad MID

AF:

0.111

Gnomad NFE

AF:

0.220

Gnomad OTH

AF:

0.193

GnomAD2 exomes

AF:

0.208

AC:

51693

AN:

248354

AF XY:

0.207

show subpopulations

Gnomad AFR exome

AF:

0.229

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.224

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.213

AC:

311105

AN:

1461578

Hom.:

33970

Cov.:

AF XY:

0.211

AC XY:

153463

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.233

AC:

7808

AN:

33478

American (AMR)

AF:

0.118

AC:

5273

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

6968

AN:

26134

East Asian (EAS)

AF:

0.179

AC:

7118

AN:

39700

South Asian (SAS)

AF:

0.160

AC:

13841

AN:

86256

European-Finnish (FIN)

AF:

0.297

AC:

15794

AN:

53220

Middle Eastern (MID)

AF:

0.128

AC:

736

AN:

5768

European-Non Finnish (NFE)

AF:

0.217

AC:

241302

AN:

1111916

Other (OTH)

AF:

0.203

AC:

12265

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

15184

30369

45553

60738

75922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8264

16528

24792

33056

41320

<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:

0.218

AC:

33088

AN:

152114

Hom.:

3717

Cov.:

AF XY:

0.216

AC XY:

16084

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.228

AC:

9474

AN:

41492

American (AMR)

AF:

0.151

AC:

2312

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

917

AN:

3470

East Asian (EAS)

AF:

0.197

AC:

1013

AN:

5150

South Asian (SAS)

AF:

0.159

AC:

766

AN:

4826

European-Finnish (FIN)

AF:

0.287

AC:

3037

AN:

10592

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.220

AC:

14941

AN:

67978

Other (OTH)

AF:

0.193

AC:

407

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1353

2706

4060

5413

6766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.204

Hom.:

5708

Bravo

AF:

0.210

Asia WGS

AF:

0.169

AC:

591

AN:

3478

EpiCase

AF:

0.205

EpiControl

AF:

0.204

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Department of Ophthalmology and Visual Sciences Kyoto University

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Apr 10, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

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

- -

Isolated microphthalmia 6

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.4

(source)

DANN

Benign

0.93

PhyloP100

1.4

Mutation Taster

=292/8

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