chr11-86946478-A-G

Position:

chr11-86946478-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012193.4(FZD4):c.*4664T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 152,044 control chromosomes in the GnomAD database, including 24,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 24796 hom., cov: 32)

Exomes 𝑓: 0.53 ( 7 hom. )

Consequence

FZD4
NM_012193.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.286

Variant links:

Genes affected

FZD4 (HGNC:4042): (frizzled class receptor 4) This gene is a member of the frizzled gene family. Members of this family encode seven-transmembrane domain proteins that are receptors for the Wingless type MMTV integration site family of signaling proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway. This protein may play a role as a positive regulator of the Wingless type MMTV integration site signaling pathway. A transcript variant retaining intronic sequence and encoding a shorter isoform has been described, however, its expression is not supported by other experimental evidence. [provided by RefSeq, Jul 2008]

FZD4 links:

PRSS23 (HGNC:14370): (serine protease 23) This gene encodes a conserved member of the trypsin family of serine proteases. Mouse studies found a decrease of mRNA levels of this gene after ovulation was induced. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

PRSS23 links:

PRSS23 (HGNC:):

PRSS23 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 11-86946478-A-G is Benign according to our data. Variant chr11-86946478-A-G is described in ClinVar as [Benign]. Clinvar id is 306335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
FZD4	NM_012193.4 linkuse as main transcript	c.*4664T>C	3_prime_UTR_variant	2/2	ENST00000531380.2	NP_036325.2	Q9ULV1
PRSS23	NR_120591.3 linkuse as main transcript	n.435-3878A>G	intron_variant
PRSS23	NR_120592.2 linkuse as main transcript	n.328-4738A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FZD4	ENST00000531380 linkuse as main transcript	c.*4664T>C		3_prime_UTR_variant	2/2	1	NM_012193.4	ENSP00000434034.1		Q9ULV1

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86079

AN:

151870

Hom.:

24795

Cov.:

show subpopulations

Gnomad AFR

AF:

0.466

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.578

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.570

Gnomad MID

AF:

0.691

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.606

GnomAD4 exome

AF:

0.534

AC:

AN:

Hom.:

Cov.:

AF XY:

0.536

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.625

Gnomad4 NFE exome

AF:

0.525

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.567

AC:

86102

AN:

151986

Hom.:

24796

Cov.:

AF XY:

0.562

AC XY:

41773

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.466

Gnomad4 AMR

AF:

0.578

Gnomad4 ASJ

AF:

0.655

Gnomad4 EAS

AF:

0.435

Gnomad4 SAS

AF:

0.498

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.631

Gnomad4 OTH

AF:

0.598

Alfa

AF:

0.618

Hom.:

58691

Bravo

AF:

0.565

Asia WGS

AF:

0.469

AC:

1632

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Exudative vitreoretinopathy 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.4

DANN

Benign

0.75

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

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