11-119346544-C-T

Variant names:

• chr11-119346544-C-T
• rs883247
• NM_031433.4:c.-31G>A

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.-31G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,611,446 control chromosomes in the GnomAD database, including 278,721 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25158 hom., cov: 32)
  • Exomes 𝑓: 0.59 (253563 hom.)
• Consequence: MFRP NM_031433.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.929
• Publications: 20 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=-0.76).
• BP6: Variant 11-119346544-C-T is Benign according to our data. Variant chr11-119346544-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 302982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4	c.-31G>A		5_prime_UTR_variant	Exon 1 of 15	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-2667G>A		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.-31G>A		5_prime_UTR_variant	Exon 1 of 15	1	NM_031433.4	ENSP00000481824.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86943 AN: 151770 Hom.: 25128 Cov.: 32

Gnomad AFR AF: 0.532

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.737

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.598

GnomAD2 exomes AF: 0.593 AC: 146964 AN: 248016 AF XY: 0.598

Gnomad AFR exome AF: 0.537

Gnomad AMR exome AF: 0.569

Gnomad ASJ exome AF: 0.550

Gnomad EAS exome AF: 0.730

Gnomad FIN exome AF: 0.524

Gnomad NFE exome AF: 0.583

Gnomad OTH exome AF: 0.599

GnomAD4 exome AF: 0.588 AC: 858187 AN: 1459558 Hom.: 253563 Cov.: 36 AF XY: 0.591 AC XY: 429085 AN XY: 726154

African (AFR) AF: 0.535 AC: 17890 AN: 33438

American (AMR) AF: 0.573 AC: 25617 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 14493 AN: 26114

East Asian (EAS) AF: 0.736 AC: 29207 AN: 39694

South Asian (SAS) AF: 0.663 AC: 57185 AN: 86196

European-Finnish (FIN) AF: 0.528 AC: 28125 AN: 53282

Middle Eastern (MID) AF: 0.663 AC: 3612 AN: 5450

European-Non Finnish (NFE) AF: 0.582 AC: 645907 AN: 1110410

Other (OTH) AF: 0.600 AC: 36151 AN: 60286

GnomAD4 genome AF: 0.573 AC: 87017 AN: 151888 Hom.: 25158 Cov.: 32 AF XY: 0.575 AC XY: 42700 AN XY: 74232

African (AFR) AF: 0.532 AC: 22020 AN: 41402

American (AMR) AF: 0.548 AC: 8360 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1976 AN: 3472

East Asian (EAS) AF: 0.737 AC: 3793 AN: 5148

South Asian (SAS) AF: 0.672 AC: 3234 AN: 4814

European-Finnish (FIN) AF: 0.543 AC: 5739 AN: 10572

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39776 AN: 67922

Other (OTH) AF: 0.600 AC: 1262 AN: 2104

Alfa AF: 0.587 Hom.: 90027

Bravo AF: 0.575

Asia WGS AF: 0.710 AC: 2466 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	3.7
DANN	Benign	0.83
PhyloP100		-0.93
PromoterAI		0.0038	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: rs883247; hg19: chr11-119217254; COSMIC: COSV64128232; COSMIC: COSV64128232;