rs3814759

Variant names:

• chr11-119346870-C-T
• rs3814759
• NM_031433.4:c.-357G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031433.4(MFRP):​c.-357G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,684 control chromosomes in the GnomAD database, including 25,763 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (25763 hom., cov: 34)
• Consequence: MFRP NM_031433.4 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.53
• Publications: 6 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-119346870-C-T is Benign according to our data. Variant chr11-119346870-C-T is described in ClinVar as Benign. ClinVar VariationId is 1250347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.72 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MFRP	NM_031433.4	MANE Select	c.-357G>A		upstream_gene	N/A	NP_113621.1	Q9BY79-1
	C1QTNF5	NM_015645.5		c.-2993G>A		upstream_gene	N/A	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.-357G>A		upstream_gene	N/A	ENSP00000481824.1	Q9BY79-1
	MFRP	ENST00000360167.4	TSL:2	c.-357G>A		upstream_gene	N/A	ENSP00000353291.4	Q9BY79-2

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88074 AN: 151566 Hom.: 25737 Cov.: 34

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.589

Gnomad OTH AF: 0.602

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.581 AC: 88145 AN: 151684 Hom.: 25763 Cov.: 34 AF XY: 0.583 AC XY: 43236 AN XY: 74156

African (AFR) AF: 0.553 AC: 22744 AN: 41106

American (AMR) AF: 0.552 AC: 8433 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.573 AC: 1989 AN: 3470

East Asian (EAS) AF: 0.739 AC: 3824 AN: 5172

South Asian (SAS) AF: 0.676 AC: 3253 AN: 4814

European-Finnish (FIN) AF: 0.544 AC: 5751 AN: 10572

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

European-Non Finnish (NFE) AF: 0.589 AC: 40019 AN: 67950

Other (OTH) AF: 0.604 AC: 1275 AN: 2112

Alfa AF: 0.577 Hom.: 3906

Bravo AF: 0.583

Asia WGS AF: 0.714 AC: 2481 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.71
PhyloP100		-4.5
PromoterAI		0.035	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs3814759; hg19: chr11-119217580;