chr11-119339269-T-A

Position:

• chr11-119339269-T-A

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.*1690A>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 0.139 in 1,558,354 control chromosomes in the GnomAD database, including 16,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2306 hom., cov: 32)
  • Exomes 𝑓: 0.14 (14138 hom.)
• Consequence: MFRP NM_031433.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.317

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 11-119339269-T-A is Benign according to our data. Variant chr11-119339269-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 302922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
C1QTNF5	NM_001278431.2	c.*62A>T		3_prime_UTR_variant	3/3	ENST00000528368.3
MFRP	NM_031433.4	c.*1690A>T		3_prime_UTR_variant	15/15	ENST00000619721.6
C1QTNF5	NM_015645.5	c.*62A>T		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
C1QTNF5	ENST00000528368.3	c.*62A>T		3_prime_UTR_variant	3/3	1	NM_001278431.2	P1
MFRP	ENST00000619721.6	c.*1690A>T		3_prime_UTR_variant	15/15	1	NM_031433.4	P1
C1QTNF5	ENST00000530681.2	c.*62A>T		3_prime_UTR_variant	2/2	1		P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24673 AN: 151884 Hom.: 2303 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.0357

Gnomad SAS AF: 0.0577

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.161

GnomAD4 exome AF: 0.137 AC: 192260 AN: 1406352 Hom.: 14138 Cov.: 28 AF XY: 0.134 AC XY: 93052 AN XY: 695350

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.0780

Gnomad4 ASJ exome AF: 0.0991

Gnomad4 EAS exome AF: 0.0495

Gnomad4 SAS exome AF: 0.0599

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.134

GnomAD4 genome AF: 0.163 AC: 24702 AN: 152002 Hom.: 2306 Cov.: 32 AF XY: 0.162 AC XY: 12028 AN XY: 74318

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.0352

Gnomad4 SAS AF: 0.0580

Gnomad4 FIN AF: 0.197

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.159

Alfa AF: 0.149 Hom.: 257

Bravo AF: 0.162

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Isolated microphthalmia 6 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinal degeneration Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.7
DANN	Benign	0.73

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: rs9640; hg19: chr11-119209979;