rs883245

Variant names:

• chr11-119346601-G-A
• rs883245
• NM_031433.4:c.-88C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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 premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.252
• Publications: 14 publications found

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: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 Gene-Disease associations (from GenCC):

• late-onset retinal degeneration

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 302987.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
MFRP	NM_031433.4	c.-88C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 15	ENST00000619721.6	NP_113621.1
MFRP	NM_031433.4	c.-88C>T		5_prime_UTR_variant	Exon 1 of 15	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-2724C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 15		NP_056460.1
C1QTNF5	NM_015645.5	c.-2724C>T		5_prime_UTR_variant	Exon 1 of 15		NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.-88C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 15	1	NM_031433.4	ENSP00000481824.1
MFRP	ENST00000619721.6	c.-88C>T		5_prime_UTR_variant	Exon 1 of 15	1	NM_031433.4	ENSP00000481824.1

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

African (AFR) AF: 0.437 AC: 12526 AN: 28680

American (AMR) AF: 0.537 AC: 23092 AN: 42970

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 13033 AN: 24532

East Asian (EAS) AF: 0.735 AC: 28338 AN: 38536

South Asian (SAS) AF: 0.636 AC: 51520 AN: 81026

European-Finnish (FIN) AF: 0.477 AC: 24928 AN: 52266

Middle Eastern (MID) AF: 0.650 AC: 2577 AN: 3964

European-Non Finnish (NFE) AF: 0.518 AC: 465037 AN: 898258

Other (OTH) AF: 0.545 AC: 28530 AN: 52326

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

African (AFR) AF: 0.432 AC: 17882 AN: 41420

American (AMR) AF: 0.512 AC: 7821 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1888 AN: 3468

East Asian (EAS) AF: 0.734 AC: 3794 AN: 5168

South Asian (SAS) AF: 0.647 AC: 3115 AN: 4816

European-Finnish (FIN) AF: 0.497 AC: 5254 AN: 10562

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.514 AC: 34903 AN: 67962

Other (OTH) AF: 0.538 AC: 1138 AN: 2114

Alfa AF: 0.491 Hom.: 6559

Bravo AF: 0.504

Asia WGS AF: 0.678 AC: 2353 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Isolated microphthalmia 6 Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinal degeneration Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.3
DANN	Benign	0.60
PhyloP100		-0.25
PromoterAI		-0.038	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs883245; hg19: chr11-119217311; COSMIC: COSV64128586; COSMIC: COSV64128586;