11-119344336-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_031433.4(MFRP):c.954G>A(p.Leu318Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 1,613,670 control chromosomes in the GnomAD database, including 2,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.044 ( 191 hom., cov: 31)

Exomes 𝑓: 0.051 ( 2451 hom. )

Consequence

MFRP
NM_031433.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0520

Publications

12 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 11-119344336-C-T is Benign according to our data. Variant chr11-119344336-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 302959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.052 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4 link	c.954G>A	p.Leu318Leu	synonymous_variant	Exon 8 of 15	ENST00000619721.6	NP_113621.1	Q9BY79-1
C1QTNF5	NM_015645.5 link	c.-1683G>A		5_prime_UTR_variant	Exon 8 of 15		NP_056460.1	Q9BXJ0A0A024R3F8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6 link	c.954G>A	p.Leu318Leu	synonymous_variant	Exon 8 of 15	1	NM_031433.4	ENSP00000481824.1		Q9BY79-1
MFRP	ENST00000360167.4 link	c.898+296G>A		intron_variant	Intron 7 of 9	2		ENSP00000353291.4		Q9BY79-2

Frequencies

GnomAD3 genomes

AF:

0.0440

AC:

6682

AN:

151934

Hom.:

191

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0204

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.0376

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.0979

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0482

Gnomad OTH

AF:

0.0450

GnomAD2 exomes

AF:

0.0547

AC:

13585

AN:

248470

AF XY:

0.0601

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.0589

Gnomad EAS exome

AF:

0.0398

Gnomad FIN exome

AF:

0.0922

Gnomad NFE exome

AF:

0.0472

Gnomad OTH exome

AF:

0.0563

GnomAD4 exome

AF:

0.0514

AC:

75090

AN:

1461618

Hom.:

2451

Cov.:

AF XY:

0.0539

AC XY:

39187

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.0209

AC:

700

AN:

33478

American (AMR)

AF:

0.0156

AC:

697

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0566

AC:

1480

AN:

26132

East Asian (EAS)

AF:

0.0364

AC:

1445

AN:

39700

South Asian (SAS)

AF:

0.125

AC:

10773

AN:

86236

European-Finnish (FIN)

AF:

0.0875

AC:

4670

AN:

53388

Middle Eastern (MID)

AF:

0.0645

AC:

372

AN:

5768

European-Non Finnish (NFE)

AF:

0.0465

AC:

51684

AN:

1111810

Other (OTH)

AF:

0.0541

AC:

3269

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

4180

8361

12541

16722

20902

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0439

AC:

6680

AN:

152052

Hom.:

191

Cov.:

AF XY:

0.0481

AC XY:

3575

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.0227

AC:

943

AN:

41466

American (AMR)

AF:

0.0204

AC:

311

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

184

AN:

3472

East Asian (EAS)

AF:

0.0373

AC:

192

AN:

5150

South Asian (SAS)

AF:

0.124

AC:

598

AN:

4818

European-Finnish (FIN)

AF:

0.0979

AC:

1033

AN:

10552

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0482

AC:

3276

AN:

67998

Other (OTH)

AF:

0.0473

AC:

100

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

306

612

919

1225

1531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0436

Hom.:

275

Bravo

AF:

0.0339

Asia WGS

AF:

0.0890

AC:

309

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

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

- -

May 05, 2021

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

- -

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

-0.45

CADD

Benign

7.0

(source)

DANN

Benign

0.86

PhyloP100

0.052

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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11-119344336-C-T

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