chr11-119344455-C-T

Variant names:

• chr11-119344455-C-T
• rs10790289
• NM_031433.4:c.899-64G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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]

C1QTNF5 Gene-Disease associations (from GenCC):

• late-onset retinal degeneration

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MFRP	NM_031433.4	c.899-64G>A		intron_variant	Intron 7 of 14	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-1738-64G>A		intron_variant	Intron 7 of 14		NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.899-64G>A		intron_variant	Intron 7 of 14	1	NM_031433.4	ENSP00000481824.1
MFRP	ENST00000360167.4	c.898+177G>A		intron_variant	Intron 7 of 9	2		ENSP00000353291.4
MFRP	ENST00000529147.2	n.*177G>A		downstream_gene_variant		5

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

African (AFR) AF: 0.444 AC: 14280 AN: 32190

American (AMR) AF: 0.726 AC: 30005 AN: 41338

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 10733 AN: 25530

East Asian (EAS) AF: 0.435 AC: 16777 AN: 38524

South Asian (SAS) AF: 0.512 AC: 42962 AN: 83850

European-Finnish (FIN) AF: 0.552 AC: 28762 AN: 52142

Middle Eastern (MID) AF: 0.458 AC: 2586 AN: 5652

European-Non Finnish (NFE) AF: 0.512 AC: 544363 AN: 1063034

Other (OTH) AF: 0.500 AC: 29155 AN: 58332

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

African (AFR) AF: 0.449 AC: 18594 AN: 41384

American (AMR) AF: 0.628 AC: 9574 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1481 AN: 3468

East Asian (EAS) AF: 0.392 AC: 2010 AN: 5130

South Asian (SAS) AF: 0.518 AC: 2491 AN: 4810

European-Finnish (FIN) AF: 0.540 AC: 5684 AN: 10518

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.513 AC: 34861 AN: 67942

Other (OTH) AF: 0.501 AC: 1057 AN: 2108

Alfa AF: 0.512 Hom.: 63275

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.55
PhyloP100		0.0020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10790289; hg19: chr11-119215165;