11-119346601-G-A

Variant names:

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.-88C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,374,554 control chromosomes in the GnomAD database, including 193,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.50 ( 19730 hom., cov: 32)

Exomes 𝑓: 0.53 ( 174007 hom. )

Consequence

MFRP
NM_031433.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.252

Publications

14 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-119346601-G-A is Benign according to our data. Variant chr11-119346601-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 302987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031433.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MFRP	NM_031433.4	MANE Select	c.-88C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_113621.1
MFRP	NM_031433.4	MANE Select	c.-88C>T	5_prime_UTR	Exon 1 of 15	NP_113621.1
C1QTNF5	NM_015645.5		c.-2724C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	NP_056460.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MFRP	ENST00000619721.6	TSL:1 MANE Select	c.-88C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 15	ENSP00000481824.1
MFRP	ENST00000619721.6	TSL:1 MANE Select	c.-88C>T	5_prime_UTR	Exon 1 of 15	ENSP00000481824.1
MFRP	ENST00000360167.4	TSL:2	c.-88C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000353291.4

Frequencies

GnomAD3 genomes

AF:

0.504

AC:

76536

AN:

151878

Hom.:

19709

Cov.:

show subpopulations

Gnomad AFR

AF:

0.431

Gnomad AMI

AF:

0.659

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.544

Gnomad EAS

AF:

0.734

Gnomad SAS

AF:

0.647

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.684

Gnomad NFE

AF:

0.514

Gnomad OTH

AF:

0.537

GnomAD4 exome

AF:

0.531

AC:

649581

AN:

1222558

Hom.:

174007

Cov.:

AF XY:

0.535

AC XY:

331155

AN XY:

618652

show subpopulations

African (AFR)

AF:

0.437

AC:

12526

AN:

28680

American (AMR)

AF:

0.537

AC:

23092

AN:

42970

Ashkenazi Jewish (ASJ)

AF:

0.531

AC:

13033

AN:

24532

East Asian (EAS)

AF:

0.735

AC:

28338

AN:

38536

South Asian (SAS)

AF:

0.636

AC:

51520

AN:

81026

European-Finnish (FIN)

AF:

0.477

AC:

24928

AN:

52266

Middle Eastern (MID)

AF:

0.650

AC:

2577

AN:

3964

European-Non Finnish (NFE)

AF:

0.518

AC:

465037

AN:

898258

Other (OTH)

AF:

0.545

AC:

28530

AN:

52326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

16120

32240

48361

64481

80601

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12362

24724

37086

49448

61810

<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:

0.504

AC:

76600

AN:

151996

Hom.:

19730

Cov.:

AF XY:

0.510

AC XY:

37858

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.432

AC:

17882

AN:

41420

American (AMR)

AF:

0.512

AC:

7821

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.544

AC:

1888

AN:

3468

East Asian (EAS)

AF:

0.734

AC:

3794

AN:

5168

South Asian (SAS)

AF:

0.647

AC:

3115

AN:

4816

European-Finnish (FIN)

AF:

0.497

AC:

5254

AN:

10562

Middle Eastern (MID)

AF:

0.697

AC:

205

AN:

294

European-Non Finnish (NFE)

AF:

0.514

AC:

34903

AN:

67962

Other (OTH)

AF:

0.538

AC:

1138

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1915

3830

5746

7661

9576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

696

1392

2088

2784

3480

<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:

0.491

Hom.:

6559

Bravo

AF:

0.504

Asia WGS

AF:

0.678

AC:

2353

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely 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

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

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.3

(source)

DANN

Benign

0.60

PhyloP100

-0.25

PromoterAI

-0.038

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over