chr11-119344061-A-G

Position:

• chr11-119344061-A-G

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.976-97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,498,876 control chromosomes in the GnomAD database, including 248,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19797 hom., cov: 29)
  • Exomes 𝑓: 0.58 (228462 hom.)
• Consequence: MFRP NM_031433.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.06

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=-0.88).
• BP6: Variant 11-119344061-A-G is Benign according to our data. Variant chr11-119344061-A-G is described in ClinVar as [Benign]. Clinvar id is 1229543.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFRP	NM_031433.4	c.976-97T>C		intron_variant		ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-1661-97T>C		intron_variant			NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.976-97T>C		intron_variant		1	NM_031433.4	ENSP00000481824.1
MFRP	ENST00000360167.4	c.898+571T>C		intron_variant		2		ENSP00000353291.4

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74083 AN: 151212 Hom.: 19808 Cov.: 29

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.625

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.577 AC: 777904 AN: 1347544 Hom.: 228462 AF XY: 0.579 AC XY: 390923 AN XY: 674898

Gnomad4 AFR exome AF: 0.243

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.462

Gnomad4 EAS exome AF: 0.333

Gnomad4 SAS exome AF: 0.628

Gnomad4 FIN exome AF: 0.611

Gnomad4 NFE exome AF: 0.595

Gnomad4 OTH exome AF: 0.548

GnomAD4 genome AF: 0.489 AC: 74070 AN: 151332 Hom.: 19797 Cov.: 29 AF XY: 0.495 AC XY: 36553 AN XY: 73910

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.468

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.641

Gnomad4 FIN AF: 0.625

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.500

Alfa AF: 0.561 Hom.: 26381

Bravo AF: 0.469

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs948413; hg19: chr11-119214771;