chr11-119342593-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_031433.4(MFRP):c.1387+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,612,606 control chromosomes in the GnomAD database, including 16,943 homozygotes. In-silico tool predicts 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 (★★).

Frequency

Genomes: 𝑓 0.10 ( 1434 hom., cov: 33)

Exomes 𝑓: 0.10 ( 15509 hom. )

Consequence

MFRP
NM_031433.4 splice_region, intron

Scores

Splicing: ADA: 0.0001498

Clinical Significance

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

Conservation

PhyloP100: 0.401

Publications

16 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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 11-119342593-C-T is Benign according to our data. Variant chr11-119342593-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4 link	c.1387+3G>A		splice_region_variant, intron_variant	Intron 11 of 14	ENST00000619721.6	NP_113621.1	Q9BY79-1
C1QTNF5	NM_015645.5 link	c.-1250+3G>A		splice_region_variant, intron_variant	Intron 11 of 14		NP_056460.1	Q9BXJ0A0A024R3F8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MFRP	ENST00000619721.6 link	c.1387+3G>A	splice_region_variant, intron_variant	Intron 11 of 14	1	NM_031433.4	ENSP00000481824.1	Q9BY79-1
MFRP	ENST00000360167.4 link	c.1161+3G>A	splice_region_variant, intron_variant	Intron 9 of 9	2		ENSP00000353291.4	Q9BY79-2
MFRP	ENST00000449574.7 link	c.256+3G>A	splice_region_variant, intron_variant	Intron 2 of 3	5		ENSP00000391664.3	A0A0X1KG76

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15598

AN:

151934

Hom.:

1431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0699

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.0989

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0699

Gnomad OTH

AF:

0.0840

GnomAD2 exomes

AF:

0.164

AC:

39963

AN:

243588

AF XY:

0.171

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.0436

Gnomad EAS exome

AF:

0.437

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.0691

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.104

AC:

151905

AN:

1460554

Hom.:

15509

Cov.:

AF XY:

0.112

AC XY:

81524

AN XY:

726552

show subpopulations

African (AFR)

AF:

0.0639

AC:

2140

AN:

33478

American (AMR)

AF:

0.208

AC:

9263

AN:

44560

Ashkenazi Jewish (ASJ)

AF:

0.0450

AC:

1175

AN:

26104

East Asian (EAS)

AF:

0.401

AC:

15915

AN:

39668

South Asian (SAS)

AF:

0.408

AC:

35124

AN:

86182

European-Finnish (FIN)

AF:

0.0989

AC:

5214

AN:

52726

Middle Eastern (MID)

AF:

0.0817

AC:

471

AN:

5768

European-Non Finnish (NFE)

AF:

0.0679

AC:

75467

AN:

1111742

Other (OTH)

AF:

0.118

AC:

7136

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

7218

14435

21653

28870

36088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.103

AC:

15599

AN:

152052

Hom.:

1434

Cov.:

AF XY:

0.113

AC XY:

8421

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0698

AC:

2895

AN:

41480

American (AMR)

AF:

0.151

AC:

2305

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0461

AC:

160

AN:

3470

East Asian (EAS)

AF:

0.419

AC:

2153

AN:

5144

South Asian (SAS)

AF:

0.432

AC:

2080

AN:

4814

European-Finnish (FIN)

AF:

0.0989

AC:

1049

AN:

10608

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0699

AC:

4747

AN:

67938

Other (OTH)

AF:

0.0874

AC:

184

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

663

1326

1990

2653

3316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0803

Hom.:

1438

Bravo

AF:

0.0991

Asia WGS

AF:

0.404

AC:

1403

AN:

3478

EpiCase

AF:

0.0689

EpiControl

AF:

0.0674

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

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

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

-0.26

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.40

PromoterAI

0.041

Neutral

(source)

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.020

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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chr11-119342593-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