11-119338986-C-A

Variant names:

• chr11-119338986-C-A
• rs551431328
• NM_031433.4:c.*1973G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_031433.4(MFRP):​c.*1973G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000087 in 241,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000056 (0 hom.)
• Consequence: MFRP NM_031433.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -0.0610
• Publications: 0 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):

• inherited retinal dystrophy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• late-onset retinal degeneration

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031433.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFRP	NM_031433.4	MANE Select	c.*1973G>T		3_prime_UTR	Exon 15 of 15	NP_113621.1	Q9BY79-1
	C1QTNF5	NM_001278431.2	MANE Select	c.*345G>T		3_prime_UTR	Exon 3 of 3	NP_001265360.1	Q9BXJ0
	C1QTNF5	NM_015645.5		c.*345G>T		3_prime_UTR	Exon 15 of 15	NP_056460.1	Q9BXJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFRP	ENST00000619721.6	TSL:1 MANE Select	c.*1973G>T		3_prime_UTR	Exon 15 of 15	ENSP00000481824.1	Q9BY79-1
	C1QTNF5	ENST00000528368.3	TSL:1 MANE Select	c.*345G>T		3_prime_UTR	Exon 3 of 3	ENSP00000431140.1	Q9BXJ0
	C1QTNF5	ENST00000530681.2	TSL:1	c.*345G>T		downstream_gene	N/A	ENSP00000456533.2	Q9BXJ0

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152088 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00328

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000560 AC: 5 AN: 89232 Hom.: 0 Cov.: 0 AF XY: 0.0000442 AC XY: 2 AN XY: 45244

African (AFR) AF: 0.00 AC: 0 AN: 3430

American (AMR) AF: 0.00 AC: 0 AN: 4112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

East Asian (EAS) AF: 0.000576 AC: 4 AN: 6946

South Asian (SAS) AF: 0.00 AC: 0 AN: 3020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 404

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56660

Other (OTH) AF: 0.000175 AC: 1 AN: 5720

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74406

African (AFR) AF: 0.00 AC: 0 AN: 41516

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68008

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Isolated microphthalmia 5 (1)
-	1	-	Late-onset retinal degeneration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.83
PhyloP100		-0.061

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: rs551431328; hg19: chr11-119209696;