rs36015759

Positions:

Variant summary

Our verdict is Benign. Variant got -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 (★★). Synonymous variant affecting the same amino acid position (i.e. YP164F?) has been classified as Likely pathogenic.

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

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 links:

MFRP (HGNC:):

MFRP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 143157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119345569-G-A is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
MFRP	NM_031433.4 linkuse as main transcript	c.492C>T	p.Tyr164Tyr	synonymous_variant	5/15	ENST00000619721.6	NP_113621.1	Q9BY79-1
C1QTNF5	NM_015645.5 linkuse as main transcript	c.-2145C>T		5_prime_UTR_variant	5/15		NP_056460.1	Q9BXJ0A0A024R3F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6 linkuse as main transcript	c.492C>T	p.Tyr164Tyr	synonymous_variant	5/15	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

GnomAD3 exomes

AF:

0.208

AC:

51693

AN:

248354

Hom.:

5867

AF XY:

0.207

AC XY:

27853

AN XY:

134588

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 SAS exome

AF:

0.163

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

Gnomad4 AFR exome

AF:

0.233

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.267

Gnomad4 EAS exome

AF:

0.179

Gnomad4 SAS exome

AF:

0.160

Gnomad4 FIN exome

AF:

0.297

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.203

GnomAD4 genome

AF:

0.218

AC:

33088

AN:

152114

Hom.:

3717

Cov.:

AF XY:

0.216

AC XY:

16084

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.228

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.197

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.287

Gnomad4 NFE

AF:

0.220

Gnomad4 OTH

AF:

0.193

Alfa

AF:

0.195

Hom.:

1276

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 10, 2020	- -
Likely benign, no assertion criteria provided	literature only	Department of Ophthalmology and Visual Sciences Kyoto University	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 24, 2014	- -

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

- -

Isolated microphthalmia 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.4

DANN

Benign

0.93

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over