11-119345521-A-G

Position:

• chr11-119345521-A-G

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.540T>C​(p.His180=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 1,613,992 control chromosomes in the GnomAD database, including 725,449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64584 hom., cov: 32)
  • Exomes 𝑓: 0.95 (660865 hom.)
• Consequence: MFRP NM_031433.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -2.25

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=-0.96).
• BP6: Variant 11-119345521-A-G is Benign according to our data. Variant chr11-119345521-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 167297.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119345521-A-G is described in Lovd as [Benign]. Variant chr11-119345521-A-G is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-2.25 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFRP	NM_031433.4	c.540T>C	p.His180=	synonymous_variant	5/15	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-2097T>C		5_prime_UTR_variant	5/15		NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.540T>C	p.His180=	synonymous_variant	5/15	1	NM_031433.4	ENSP00000481824	P1
MFRP	ENST00000360167.4	c.540T>C	p.His180=	synonymous_variant	5/10	2		ENSP00000353291
MFRP	ENST00000529147.2	n.503T>C		non_coding_transcript_exon_variant	4/6	5
MFRP	ENST00000634542.1	c.*131T>C		3_prime_UTR_variant, NMD_transcript_variant	4/5	3		ENSP00000488979

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139959 AN: 152098 Hom.: 64526 Cov.: 32

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.913

Gnomad EAS AF: 0.862

Gnomad SAS AF: 0.964

Gnomad FIN AF: 0.938

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.960

Gnomad OTH AF: 0.917

GnomAD3 exomes AF: 0.932 AC: 231719 AN: 248740 Hom.: 108205 AF XY: 0.938 AC XY: 126394 AN XY: 134738

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.859

Gnomad ASJ exome AF: 0.918

Gnomad EAS exome AF: 0.870

Gnomad SAS exome AF: 0.971

Gnomad FIN exome AF: 0.938

Gnomad NFE exome AF: 0.962

Gnomad OTH exome AF: 0.932

GnomAD4 exome AF: 0.950 AC: 1389338 AN: 1461776 Hom.: 660865 Cov.: 65 AF XY: 0.952 AC XY: 692158 AN XY: 727184

Gnomad4 AFR exome AF: 0.864

Gnomad4 AMR exome AF: 0.862

Gnomad4 ASJ exome AF: 0.917

Gnomad4 EAS exome AF: 0.873

Gnomad4 SAS exome AF: 0.971

Gnomad4 FIN exome AF: 0.940

Gnomad4 NFE exome AF: 0.960

Gnomad4 OTH exome AF: 0.941

GnomAD4 genome AF: 0.920 AC: 140073 AN: 152216 Hom.: 64584 Cov.: 32 AF XY: 0.919 AC XY: 68413 AN XY: 74432

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.913

Gnomad4 EAS AF: 0.862

Gnomad4 SAS AF: 0.964

Gnomad4 FIN AF: 0.938

Gnomad4 NFE AF: 0.960

Gnomad4 OTH AF: 0.915

Alfa AF: 0.940 Hom.: 50187

Bravo AF: 0.911

Asia WGS AF: 0.917 AC: 3191 AN: 3478

EpiCase AF: 0.959

EpiControl AF: 0.959

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

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	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Isolated microphthalmia 6 Benign:1

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

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.31
DANN	Benign	0.59

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: rs2510143; hg19: chr11-119216231; COSMIC: COSV64128971; COSMIC: COSV64128971;