11-119343072-A-G

Variant names:

• chr11-119343072-A-G
• rs948411
• NM_031433.4:c.1125-69T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031433.4(MFRP):​c.1125-69T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MFRP NM_031433.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 4 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4	c.1125-69T>C		intron_variant	Intron 9 of 14	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-1512-69T>C		intron_variant	Intron 9 of 14		NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.1125-69T>C		intron_variant	Intron 9 of 14	1	NM_031433.4	ENSP00000481824.1
MFRP	ENST00000360167.4	c.899-69T>C		intron_variant	Intron 7 of 9	2		ENSP00000353291.4
MFRP	ENST00000449574.7	c.-94T>C		upstream_gene_variant		5		ENSP00000391664.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1389156 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 686196

African (AFR) AF: 0.00 AC: 0 AN: 31878

American (AMR) AF: 0.00 AC: 0 AN: 36194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25206

East Asian (EAS) AF: 0.00 AC: 0 AN: 36338

South Asian (SAS) AF: 0.00 AC: 0 AN: 79550

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078390

Other (OTH) AF: 0.00 AC: 0 AN: 57906

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.90
PhyloP100		-0.057
PromoterAI		-0.033	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs948411; hg19: chr11-119213782;