rs948414

Positions:

• chr11-119344088-T-C

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.976-124A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 1,292,110 control chromosomes in the GnomAD database, including 247,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.60 (27378 hom., cov: 30)
  • Exomes 𝑓: 0.62 (219965 hom.)
• Consequence: MFRP NM_031433.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.451

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:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-119344088-T-C is Benign according to our data. Variant chr11-119344088-T-C is described in ClinVar as [Benign]. Clinvar id is 1231094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFRP	NM_031433.4	c.976-124A>G		intron_variant		ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-1661-124A>G		intron_variant			NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.976-124A>G		intron_variant		1	NM_031433.4	ENSP00000481824	P1
MFRP	ENST00000360167.4	c.898+544A>G		intron_variant		2		ENSP00000353291

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90384 AN: 151658 Hom.: 27345 Cov.: 30

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.600

GnomAD4 exome AF: 0.618 AC: 704731 AN: 1140332 Hom.: 219965 AF XY: 0.619 AC XY: 357634 AN XY: 577684

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.509

Gnomad4 EAS exome AF: 0.573

Gnomad4 SAS exome AF: 0.661

Gnomad4 FIN exome AF: 0.716

Gnomad4 NFE exome AF: 0.613

Gnomad4 OTH exome AF: 0.601

GnomAD4 genome AF: 0.596 AC: 90459 AN: 151778 Hom.: 27378 Cov.: 30 AF XY: 0.603 AC XY: 44763 AN XY: 74174

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.513

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.613

Gnomad4 OTH AF: 0.595

Alfa AF: 0.611 Hom.: 39227

Bravo AF: 0.587

Asia WGS AF: 0.601 AC: 2091 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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.86

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: rs948414; hg19: chr11-119214798;