11-119346745-C-T

Variant names:

• chr11-119346745-C-T
• rs948415
• NM_031433.4:c.-232G>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.-232G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.594 in 613,752 control chromosomes in the GnomAD database, including 109,209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25319 hom., cov: 32)
  • Exomes 𝑓: 0.60 (83890 hom.)
• Consequence: MFRP NM_031433.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.882
• Publications: 8 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=-0.86).
• BP6: Variant 11-119346745-C-T is Benign according to our data. Variant chr11-119346745-C-T is described in ClinVar as Benign. ClinVar VariationId is 1254395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.719 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFRP	NM_031433.4	MANE Select	c.-232G>A		upstream_gene	N/A	NP_113621.1
	C1QTNF5	NM_015645.5		c.-2868G>A		upstream_gene	N/A	NP_056460.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFRP	ENST00000619721.6	TSL:1 MANE Select	c.-232G>A		upstream_gene	N/A	ENSP00000481824.1
	MFRP	ENST00000360167.4	TSL:2	c.-232G>A		upstream_gene	N/A	ENSP00000353291.4
	MFRP	ENST00000526059.1	TSL:3	n.-128G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87260 AN: 151872 Hom.: 25292 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.548

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.598

GnomAD4 exome AF: 0.600 AC: 277094 AN: 461762 Hom.: 83890 AF XY: 0.604 AC XY: 148085 AN XY: 245120

African (AFR) AF: 0.545 AC: 7150 AN: 13122

American (AMR) AF: 0.565 AC: 13514 AN: 23920

Ashkenazi Jewish (ASJ) AF: 0.555 AC: 8043 AN: 14488

East Asian (EAS) AF: 0.741 AC: 22718 AN: 30662

South Asian (SAS) AF: 0.663 AC: 31798 AN: 47972

European-Finnish (FIN) AF: 0.529 AC: 15377 AN: 29062

Middle Eastern (MID) AF: 0.674 AC: 1333 AN: 1978

European-Non Finnish (NFE) AF: 0.589 AC: 161420 AN: 274228

Other (OTH) AF: 0.598 AC: 15741 AN: 26330

GnomAD4 genome AF: 0.575 AC: 87330 AN: 151990 Hom.: 25319 Cov.: 32 AF XY: 0.577 AC XY: 42827 AN XY: 74274

African (AFR) AF: 0.533 AC: 22096 AN: 41438

American (AMR) AF: 0.549 AC: 8391 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1990 AN: 3468

East Asian (EAS) AF: 0.738 AC: 3815 AN: 5166

South Asian (SAS) AF: 0.673 AC: 3244 AN: 4818

European-Finnish (FIN) AF: 0.544 AC: 5741 AN: 10550

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39934 AN: 67942

Other (OTH) AF: 0.599 AC: 1263 AN: 2110

Alfa AF: 0.568 Hom.: 3136

Bravo AF: 0.577

Asia WGS AF: 0.712 AC: 2473 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: 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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.66
PhyloP100		-0.88
PromoterAI		-0.0098	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs948415; hg19: chr11-119217455;