11-119344455-C-T

Position:

• chr11-119344455-C-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.899-64G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 1,552,414 control chromosomes in the GnomAD database, including 206,370 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19486 hom., cov: 31)
  • Exomes 𝑓: 0.51 (186884 hom.)
• Consequence: MFRP NM_031433.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00200

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=-0.81).
• BP6: Variant 11-119344455-C-T is Benign according to our data. Variant chr11-119344455-C-T is described in ClinVar as [Benign]. Clinvar id is 1224886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFRP	NM_031433.4	c.899-64G>A		intron_variant		ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-1738-64G>A		intron_variant			NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.899-64G>A		intron_variant		1	NM_031433.4	ENSP00000481824	P1
MFRP	ENST00000360167.4	c.898+177G>A		intron_variant		2		ENSP00000353291

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76311 AN: 151704 Hom.: 19480 Cov.: 31

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.392

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.513

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.514 AC: 719623 AN: 1400592 Hom.: 186884 Cov.: 23 AF XY: 0.513 AC XY: 358081 AN XY: 698040

Gnomad4 AFR exome AF: 0.444

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.420

Gnomad4 EAS exome AF: 0.435

Gnomad4 SAS exome AF: 0.512

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.512

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.503 AC: 76336 AN: 151822 Hom.: 19486 Cov.: 31 AF XY: 0.504 AC XY: 37361 AN XY: 74154

Gnomad4 AFR AF: 0.449

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.392

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.513

Gnomad4 OTH AF: 0.501

Alfa AF: 0.508 Hom.: 26064

Bravo AF: 0.509

Asia WGS AF: 0.465 AC: 1617 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	-0.81
CADD	Benign	5.9
DANN	Benign	0.55

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: rs10790289; hg19: chr11-119215165;