rs883245

Positions:

• chr11-119346601-G-A
• chr11-119346601-G-C
• chr11-119346601-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031433.4(MFRP):​c.-88C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,374,554 control chromosomes in the GnomAD database, including 193,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19730 hom., cov: 32)
  • Exomes 𝑓: 0.53 (174007 hom.)
• Consequence: MFRP NM_031433.4 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.252

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-119346601-G-A is Benign according to our data. Variant chr11-119346601-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 302987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119346601-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFRP	NM_031433.4	c.-88C>T		5_prime_UTR_variant	1/15	ENST00000619721.6
C1QTNF5	NM_015645.5	c.-2724C>T		5_prime_UTR_variant	1/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFRP	ENST00000619721.6	c.-88C>T		5_prime_UTR_variant	1/15	1	NM_031433.4	P1
MFRP	ENST00000360167.4	c.-88C>T		5_prime_UTR_variant	1/10	2
MFRP	ENST00000526059.1	n.17C>T		non_coding_transcript_exon_variant	1/3	3
MFRP	ENST00000634542.1	c.-88C>T		5_prime_UTR_variant, NMD_transcript_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76536 AN: 151878 Hom.: 19709 Cov.: 32

Gnomad AFR AF: 0.431

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.537

GnomAD4 exome AF: 0.531 AC: 649581 AN: 1222558 Hom.: 174007 Cov.: 17 AF XY: 0.535 AC XY: 331155 AN XY: 618652

Gnomad4 AFR exome AF: 0.437

Gnomad4 AMR exome AF: 0.537

Gnomad4 ASJ exome AF: 0.531

Gnomad4 EAS exome AF: 0.735

Gnomad4 SAS exome AF: 0.636

Gnomad4 FIN exome AF: 0.477

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.504 AC: 76600 AN: 151996 Hom.: 19730 Cov.: 32 AF XY: 0.510 AC XY: 37858 AN XY: 74282

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.734

Gnomad4 SAS AF: 0.647

Gnomad4 FIN AF: 0.497

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.538

Alfa AF: 0.442 Hom.: 2824

Bravo AF: 0.504

Asia WGS AF: 0.678 AC: 2353 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs883245; hg19: chr11-119217311; COSMIC: COSV64128586; COSMIC: COSV64128586;