rs35885438

chr11-119344336-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_031433.4(MFRP):c.954G>A(p.Leu318=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.0520

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]

C1QTNF5 (HGNC:):

ACMG classification

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	UniProt
MFRP	NM_031433.4	c.954G>A	p.Leu318=	synonymous_variant	8/15	ENST00000619721.6
C1QTNF5	NM_015645.5	c.-1683G>A		5_prime_UTR_variant	8/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFRP	ENST00000619721.6	c.954G>A	p.Leu318=	synonymous_variant	8/15	1	NM_031433.4	P1
MFRP	ENST00000360167.4	c.898+296G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0440 AC: 6682 AN: 151934 Hom.: 191 Cov.: 31

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

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.: 33 AF XY: 0.0539 AC XY: 39187 AN XY: 727114

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.: 31 AF XY: 0.0481 AC XY: 3575 AN XY: 74286

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.: 79

Bravo AF: 0.0339

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 05, 2021

- -

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

Other links and lift over

dbSNP: rs35885438; hg19: chr11-119215046; COSMIC: COSV64128598; COSMIC: COSV64128598;