11-119344061-A-G

Variant names:

• chr11-119344061-A-G
• rs948413
• NM_031433.4:c.976-97T>C

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.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
• Publications: 9 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=-0.88).
• 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 rank	MANE	Protein	UniProt
MFRP	NM_031433.4	c.976-97T>C		intron_variant	Intron 8 of 14	ENST00000619721.6	NP_113621.1
C1QTNF5	NM_015645.5	c.-1661-97T>C		intron_variant	Intron 8 of 14		NP_056460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFRP	ENST00000619721.6	c.976-97T>C		intron_variant	Intron 8 of 14	1	NM_031433.4	ENSP00000481824.1
MFRP	ENST00000360167.4	c.898+571T>C		intron_variant	Intron 7 of 9	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

African (AFR) AF: 0.243 AC: 7646 AN: 31506

American (AMR) AF: 0.611 AC: 25944 AN: 42436

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 11653 AN: 25234

East Asian (EAS) AF: 0.333 AC: 12948 AN: 38930

South Asian (SAS) AF: 0.628 AC: 51964 AN: 82720

European-Finnish (FIN) AF: 0.611 AC: 24967 AN: 40888

Middle Eastern (MID) AF: 0.485 AC: 2515 AN: 5188

European-Non Finnish (NFE) AF: 0.595 AC: 609155 AN: 1023836

Other (OTH) AF: 0.548 AC: 31112 AN: 56806

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

African (AFR) AF: 0.267 AC: 10964 AN: 41126

American (AMR) AF: 0.570 AC: 8678 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1619 AN: 3462

East Asian (EAS) AF: 0.301 AC: 1532 AN: 5090

South Asian (SAS) AF: 0.641 AC: 3067 AN: 4786

European-Finnish (FIN) AF: 0.625 AC: 6552 AN: 10486

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40011 AN: 67854

Other (OTH) AF: 0.500 AC: 1050 AN: 2098

Alfa AF: 0.553 Hom.: 34251

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

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	-0.88
CADD	Benign	3.7
DANN	Benign	0.39
PhyloP100		-2.1
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: rs948413; hg19: chr11-119214771; COSMIC: COSV107466106; COSMIC: COSV107466106;