11-119344876-C-T

Position:

chr11-119344876-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000619721.6(MFRP):c.770G>A(p.Arg257His) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00559 in 1,613,140 control chromosomes in the GnomAD database, including 383 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R257R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.028 ( 201 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 182 hom. )

Consequence

MFRP
ENST00000619721.6 missense, splice_region

Scores

Splicing: ADA: 0.00003878

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.03

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:):

C1QTNF5 links:

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=0.0015755296).

BP6

Variant 11-119344876-C-T is Benign according to our data. Variant chr11-119344876-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 198271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119344876-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0948 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.770G>A	p.Arg257His	missense_variant, splice_region_variant	6/15	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5 linkuse as main transcript	c.-1867G>A		splice_region_variant, 5_prime_UTR_variant	6/15		NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6 linkuse as main transcript	c.770G>A	p.Arg257His	missense_variant, splice_region_variant	6/15	1	NM_031433.4	ENSP00000481824	P1	Q9BY79-1
MFRP	ENST00000360167.4 linkuse as main transcript	c.770G>A	p.Arg257His	missense_variant, splice_region_variant	6/10	2		ENSP00000353291		Q9BY79-2
MFRP	ENST00000529147.2 linkuse as main transcript	n.733G>A		splice_region_variant, non_coding_transcript_exon_variant	5/6	5
MFRP	ENST00000634542.1 linkuse as main transcript			downstream_gene_variant		3		ENSP00000488979

Frequencies

GnomAD3 genomes

AF:

0.0280

AC:

4261

AN:

152122

Hom.:

196

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0968

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00870

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00674

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.00843

AC:

2061

AN:

244618

Hom.:

AF XY:

0.00660

AC XY:

878

AN XY:

132966

show subpopulations

Gnomad AFR exome

AF:

0.0984

Gnomad AMR exome

AF:

0.00494

Gnomad ASJ exome

AF:

0.000202

Gnomad EAS exome

AF:

0.00752

Gnomad SAS exome

AF:

0.00429

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000268

Gnomad OTH exome

AF:

0.00399

GnomAD4 exome

AF:

0.00323

AC:

4715

AN:

1460900

Hom.:

182

Cov.:

AF XY:

0.00290

AC XY:

2107

AN XY:

726714

show subpopulations

Gnomad4 AFR exome

AF:

0.0970

Gnomad4 AMR exome

AF:

0.00539

Gnomad4 ASJ exome

AF:

0.000191

Gnomad4 EAS exome

AF:

0.00776

Gnomad4 SAS exome

AF:

0.00407

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.0000998

Gnomad4 OTH exome

AF:

0.00687

GnomAD4 genome

AF:

0.0282

AC:

4295

AN:

152240

Hom.:

201

Cov.:

AF XY:

0.0269

AC XY:

2006

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0973

Gnomad4 AMR

AF:

0.00869

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00675

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.00628

Hom.:

Bravo

AF:

0.0309

ESP6500AA

AF:

0.0958

AC:

421

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0102

AC:

1238

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	This variant is associated with the following publications: (PMID: 27884173, 18648522, 20981092) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 23, 2015

- -

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 29, 2024

- -

Late-onset retinal degeneration

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.15

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-2.2

N;N

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.61

.;N

REVEL

Benign

0.10

Sift

Benign

0.73

.;T

Sift4G

Benign

0.99

T;T

Polyphen

0.0

B;.

Vest4

0.14

ClinPred

0.012

GERP RS

4.9

Varity_R

0.035

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000039

dbscSNV1_RF

Benign

0.0020

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.

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