Genetic Variant NM_031433.4:c.*1753A>T (chr11-119339206-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031433.4(MFRP):c.*1753A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

MFRP
NM_031433.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.946

Publications

1 publications found

Variant links:

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]

MFRP links:

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

C1QTNF5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MFRP	NM_031433.4 link	c.*1753A>T	3_prime_UTR_variant	Exon 15 of 15	ENST00000619721.6	NP_113621.1	Q9BY79-1
C1QTNF5	NM_001278431.2 link	c.*125A>T	3_prime_UTR_variant	Exon 3 of 3	ENST00000528368.3	NP_001265360.1	Q9BXJ0A0A024R3F8
C1QTNF5	NM_015645.5 link	c.*125A>T	3_prime_UTR_variant	Exon 15 of 15		NP_056460.1	Q9BXJ0A0A024R3F8

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MFRP	ENST00000619721.6 link	c.*1753A>T	3_prime_UTR_variant	Exon 15 of 15	1	NM_031433.4	ENSP00000481824.1	Q9BY79-1
C1QTNF5	ENST00000528368.3 link	c.*125A>T	3_prime_UTR_variant	Exon 3 of 3	1	NM_001278431.2	ENSP00000431140.1	Q9BXJ0
C1QTNF5	ENST00000530681.2 link	c.*125A>T	3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000456533.2	Q9BXJ0
C1QTNF5	ENST00000525657.2 link	n.*164A>T	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000661

AC:

AN:

151226

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73858

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41206

American (AMR)

AF:

0.00

AC:

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000198

AC:

AN:

5058

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67714

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

1.8

(source)

DANN

Benign

0.61

PhyloP100

-0.95

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over