rs12421909

chr11-119345191-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031433.4(MFRP):c.642-187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0831 in 152,250 control chromosomes in the GnomAD database, including 812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.083 (812 hom., cov: 32)
• Consequence: MFRP NM_031433.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.208

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 11-119345191-C-T is Benign according to our data. Variant chr11-119345191-C-T is described in ClinVar as [Benign]. Clinvar id is 1272146.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFRP	NM_031433.4	c.642-187G>A		intron_variant		ENST00000619721.6
C1QTNF5	NM_015645.5	c.-1995-187G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFRP	ENST00000619721.6	c.642-187G>A		intron_variant		1	NM_031433.4	P1
MFRP	ENST00000360167.4	c.642-187G>A		intron_variant		2
MFRP	ENST00000634542.1	c.*233-187G>A		intron_variant, NMD_transcript_variant		3
MFRP	ENST00000529147.2	n.605-187G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0831 AC: 12642 AN: 152132 Hom.: 814 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0630

Gnomad OTH AF: 0.0774

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0831 AC: 12652 AN: 152250 Hom.: 812 Cov.: 32 AF XY: 0.0893 AC XY: 6648 AN XY: 74426

Gnomad4 AFR AF: 0.0527

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.0675

Gnomad4 NFE AF: 0.0630

Gnomad4 OTH AF: 0.0808

Alfa AF: 0.0695 Hom.: 110

Bravo AF: 0.0799

Asia WGS AF: 0.290 AC: 1005 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.91
Cadd	Benign	7.1
Dann	Benign	0.60

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: rs12421909; hg19: chr11-119215901;