rs36015759

chr11-119345569-G-Achr11-119345569-G-Cchr11-119345569-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_031433.4(MFRP):c.492C>T(p.Tyr164=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,613,692 control chromosomes in the GnomAD database, including 37,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. YP164F?) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: 𝑓 0.22 (3717 hom., cov: 32)
  • Exomes 𝑓: 0.21 (33970 hom.)
• Consequence: MFRP NM_031433.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.39

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 11-119345569-G-A is Benign according to our data. Variant chr11-119345569-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 143157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119345569-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=1.39 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFRP	NM_031433.4	c.492C>T	p.Tyr164=	synonymous_variant	5/15	ENST00000619721.6
C1QTNF5	NM_015645.5	c.-2145C>T		5_prime_UTR_variant	5/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFRP	ENST00000619721.6	c.492C>T	p.Tyr164=	synonymous_variant	5/15	1	NM_031433.4	P1
MFRP	ENST00000360167.4	c.492C>T	p.Tyr164=	synonymous_variant	5/10	2
MFRP	ENST00000529147.2	n.455C>T		non_coding_transcript_exon_variant	4/6	5
MFRP	ENST00000634542.1	c.*83C>T		3_prime_UTR_variant, NMD_transcript_variant	4/5	3

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33077 AN: 151996 Hom.: 3714 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.208 AC: 51693 AN: 248354 Hom.: 5867 AF XY: 0.207 AC XY: 27853 AN XY: 134588

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.112

Gnomad ASJ exome AF: 0.272

Gnomad EAS exome AF: 0.219

Gnomad SAS exome AF: 0.163

Gnomad FIN exome AF: 0.293

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.194

GnomAD4 exome AF: 0.213 AC: 311105 AN: 1461578 Hom.: 33970 Cov.: 60 AF XY: 0.211 AC XY: 153463 AN XY: 727098

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.160

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.218 AC: 33088 AN: 152114 Hom.: 3717 Cov.: 32 AF XY: 0.216 AC XY: 16084 AN XY: 74372

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.197

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.193

Alfa AF: 0.195 Hom.: 1276

Bravo AF: 0.210

Asia WGS AF: 0.169 AC: 591 AN: 3478

EpiCase AF: 0.205

EpiControl AF: 0.204

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 24, 2014	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 10, 2020	- -
Likely benign, no assertion criteria provided	literature only	Department of Ophthalmology and Visual Sciences Kyoto University	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	5.4
Dann	Benign	0.93

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: rs36015759; hg19: chr11-119216279; COSMIC: COSV64127956; COSMIC: COSV64127956;