rs35885438

Positions:

chr11-119344336-C-T

Variant summary

Our verdict is Benign. Variant got -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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr11-119344336-C-T is described in Lovd as [Benign]. Variant chr11-119344336-C-T is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
MFRP	NM_031433.4 linkuse as main transcript	c.954G>A	p.Leu318Leu	synonymous_variant	8/15	ENST00000619721.6	NP_113621.1	Q9BY79-1
C1QTNF5	NM_015645.5 linkuse as main transcript	c.-1683G>A		5_prime_UTR_variant	8/15		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.954G>A	p.Leu318Leu	synonymous_variant	8/15	1	NM_031433.4	ENSP00000481824.1		Q9BY79-1
MFRP	ENST00000360167.4 linkuse as main transcript	c.898+296G>A		intron_variant		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

GnomAD3 exomes

AF:

0.0547

AC:

13585

AN:

248470

Hom.:

577

AF XY:

0.0601

AC XY:

8097

AN XY:

134684

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 SAS exome

AF:

0.124

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

Gnomad4 AFR exome

AF:

0.0209

Gnomad4 AMR exome

AF:

0.0156

Gnomad4 ASJ exome

AF:

0.0566

Gnomad4 EAS exome

AF:

0.0364

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.0875

Gnomad4 NFE exome

AF:

0.0465

Gnomad4 OTH exome

AF:

0.0541

GnomAD4 genome

AF:

0.0439

AC:

6680

AN:

152052

Hom.:

191

Cov.:

AF XY:

0.0481

AC XY:

3575

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0227

Gnomad4 AMR

AF:

0.0204

Gnomad4 ASJ

AF:

0.0530

Gnomad4 EAS

AF:

0.0373

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.0979

Gnomad4 NFE

AF:

0.0482

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0444

Hom.:

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

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

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

-0.45

CADD

Benign

7.0

DANN

Benign

0.86

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