chr11-119343072-A-T

Position:

• chr11-119343072-A-T

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.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

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=-0.65).
• BP6: Variant 11-119343072-A-T is Benign according to our data. Variant chr11-119343072-A-T is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	Protein	UniProt
MFRP	NM_031433.4	c.1125-69T>A		intron_variant		ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-1512-69T>A		intron_variant			NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.1125-69T>A		intron_variant		1	NM_031433.4	ENSP00000481824.1
MFRP	ENST00000360167.4	c.899-69T>A		intron_variant		2		ENSP00000353291.4

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

Gnomad4 AFR exome AF: 0.234

Gnomad4 AMR exome AF: 0.0786

Gnomad4 ASJ exome AF: 0.102

Gnomad4 EAS exome AF: 0.0500

Gnomad4 SAS exome AF: 0.0650

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.128

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

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.0348

Gnomad4 SAS AF: 0.0599

Gnomad4 FIN AF: 0.184

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.151

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs948411; hg19: chr11-119213782;