11-119346745-C-T

Variant names:

• chr11-119346745-C-T
• rs948415
• NM_031433.4:c.-232G>A

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.-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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4	c.-232G>A		upstream_gene_variant		ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-2868G>A		upstream_gene_variant			NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.-232G>A		upstream_gene_variant		1	NM_031433.4	ENSP00000481824.1
MFRP	ENST00000360167.4	c.-232G>A		upstream_gene_variant		2		ENSP00000353291.4
MFRP	ENST00000526059.1	n.-128G>A		upstream_gene_variant		3
MFRP	ENST00000634542.1	n.-232G>A		upstream_gene_variant		3		ENSP00000488979.1

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

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.663

Gnomad4 FIN exome AF: 0.529

Gnomad4 NFE exome AF: 0.589

Gnomad4 OTH exome AF: 0.598

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

Gnomad4 AFR AF: 0.533

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.574

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.544

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.599

Alfa AF: 0.569 Hom.: 3028

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs948415; hg19: chr11-119217455;