11-119342593-C-T

Position:

chr11-119342593-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_031433.4(MFRP):c.1387+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,612,606 control chromosomes in the GnomAD database, including 16,943 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1434 hom., cov: 33)

Exomes 𝑓: 0.10 ( 15509 hom. )

Consequence

MFRP
NM_031433.4 splice_region, intron

Scores

Splicing: ADA: 0.0001498

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.401

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 11-119342593-C-T is Benign according to our data. Variant chr11-119342593-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 261962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119342593-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFRP	NM_031433.4 linkuse as main transcript	c.1387+3G>A		splice_region_variant, intron_variant		ENST00000619721.6	NP_113621.1	Q9BY79-1
C1QTNF5	NM_015645.5 linkuse as main transcript	c.-1250+3G>A		splice_region_variant, intron_variant			NP_056460.1	Q9BXJ0A0A024R3F8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
MFRP	ENST00000619721.6 linkuse as main transcript	c.1387+3G>A	splice_region_variant, intron_variant	1	NM_031433.4	ENSP00000481824.1	Q9BY79-1
MFRP	ENST00000360167.4 linkuse as main transcript	c.1161+3G>A	splice_region_variant, intron_variant	2		ENSP00000353291.4	Q9BY79-2
MFRP	ENST00000449574.7 linkuse as main transcript	c.256+3G>A	splice_region_variant, intron_variant	5		ENSP00000391664.3	A0A0X1KG76

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15598

AN:

151934

Hom.:

1431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0699

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.151

Gnomad ASJ

AF:

0.0461

Gnomad EAS

AF:

0.419

Gnomad SAS

AF:

0.433

Gnomad FIN

AF:

0.0989

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0699

Gnomad OTH

AF:

0.0840

GnomAD3 exomes

AF:

0.164

AC:

39963

AN:

243588

Hom.:

5925

AF XY:

0.171

AC XY:

22649

AN XY:

132780

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.218

Gnomad ASJ exome

AF:

0.0436

Gnomad EAS exome

AF:

0.437

Gnomad SAS exome

AF:

0.419

Gnomad FIN exome

AF:

0.100

Gnomad NFE exome

AF:

0.0691

Gnomad OTH exome

AF:

0.112

GnomAD4 exome

AF:

0.104

AC:

151905

AN:

1460554

Hom.:

15509

Cov.:

AF XY:

0.112

AC XY:

81524

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.0639

Gnomad4 AMR exome

AF:

0.208

Gnomad4 ASJ exome

AF:

0.0450

Gnomad4 EAS exome

AF:

0.401

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.0989

Gnomad4 NFE exome

AF:

0.0679

Gnomad4 OTH exome

AF:

0.118

GnomAD4 genome

AF:

0.103

AC:

15599

AN:

152052

Hom.:

1434

Cov.:

AF XY:

0.113

AC XY:

8421

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0698

Gnomad4 AMR

AF:

0.151

Gnomad4 ASJ

AF:

0.0461

Gnomad4 EAS

AF:

0.419

Gnomad4 SAS

AF:

0.432

Gnomad4 FIN

AF:

0.0989

Gnomad4 NFE

AF:

0.0699

Gnomad4 OTH

AF:

0.0874

Alfa

AF:

0.0803

Hom.:

1226

Bravo

AF:

0.0991

Asia WGS

AF:

0.404

AC:

1403

AN:

3478

EpiCase

AF:

0.0689

EpiControl

AF:

0.0674

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

- -

Isolated microphthalmia 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.92

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00015

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over