11-119343072-A-T

Variant names:

• chr11-119343072-A-T
• rs948411
• NM_031433.4:c.1125-69T>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.1125-69T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,541,070 control chromosomes in the GnomAD database, including 14,285 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1984 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12301 hom.)
• Consequence: MFRP NM_031433.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-119343072-A-T is Benign according to our data. Variant chr11-119343072-A-T is described in ClinVar as Benign. ClinVar VariationId is 1234136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4	c.1125-69T>A		intron_variant	Intron 9 of 14	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-1512-69T>A		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>A		intron_variant	Intron 9 of 14	1	NM_031433.4	ENSP00000481824.1
MFRP	ENST00000360167.4	c.899-69T>A		intron_variant	Intron 7 of 9	2		ENSP00000353291.4
MFRP	ENST00000449574.7	c.-94T>A		upstream_gene_variant		5		ENSP00000391664.3

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23083 AN: 152210 Hom.: 1979 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.0596

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.129 AC: 179411 AN: 1388742 Hom.: 12301 AF XY: 0.127 AC XY: 86803 AN XY: 686018

African (AFR) AF: 0.234 AC: 7462 AN: 31860

American (AMR) AF: 0.0786 AC: 2845 AN: 36194

Ashkenazi Jewish (ASJ) AF: 0.102 AC: 2578 AN: 25202

East Asian (EAS) AF: 0.0500 AC: 1818 AN: 36334

South Asian (SAS) AF: 0.0650 AC: 5173 AN: 79546

European-Finnish (FIN) AF: 0.176 AC: 6936 AN: 39458

Middle Eastern (MID) AF: 0.138 AC: 580 AN: 4214

European-Non Finnish (NFE) AF: 0.134 AC: 144622 AN: 1078044

Other (OTH) AF: 0.128 AC: 7397 AN: 57890

GnomAD4 genome AF: 0.152 AC: 23108 AN: 152328 Hom.: 1984 Cov.: 33 AF XY: 0.151 AC XY: 11272 AN XY: 74484

African (AFR) AF: 0.223 AC: 9274 AN: 41558

American (AMR) AF: 0.113 AC: 1735 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3472

East Asian (EAS) AF: 0.0348 AC: 181 AN: 5194

South Asian (SAS) AF: 0.0599 AC: 289 AN: 4828

European-Finnish (FIN) AF: 0.184 AC: 1949 AN: 10616

Middle Eastern (MID) AF: 0.164 AC: 48 AN: 292

European-Non Finnish (NFE) AF: 0.130 AC: 8854 AN: 68034

Other (OTH) AF: 0.151 AC: 319 AN: 2114

Alfa AF: 0.0331 Hom.: 22

Bravo AF: 0.151

Asia WGS AF: 0.0580 AC: 204 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

- -

May 13, 2021

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	-0.65
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		-0.057
PromoterAI		-0.040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;