Variant rs11063112 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020638.3(FGF23):c.*1429A>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 0.231 in 221,966 control chromosomes in the GnomAD database, including 6,476 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4401 hom., cov: 31)

Exomes 𝑓: 0.24 ( 2075 hom. )

Consequence

FGF23
NM_020638.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.305

Variant links:

Genes affected

FGF23 (HGNC:3680): (fibroblast growth factor 23) This gene encodes a member of the fibroblast growth factor family of proteins, which possess broad mitogenic and cell survival activities and are involved in a variety of biological processes. The product of this gene regulates phosphate homeostasis and transport in the kidney. The full-length, functional protein may be deactivated via cleavage into N-terminal and C-terminal chains. Mutation of this cleavage site causes autosomal dominant hypophosphatemic rickets (ADHR). Mutations in this gene are also associated with hyperphosphatemic familial tumoral calcinosis (HFTC). [provided by RefSeq, Feb 2013]

FGF23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 12-4368914-T-A is Benign according to our data. Variant chr12-4368914-T-A is described in ClinVar as [Benign]. Clinvar id is 308779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF23	NM_020638.3 linkuse as main transcript	c.*1429A>T		3_prime_UTR_variant	3/3	ENST00000237837.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF23	ENST00000237837.2 linkuse as main transcript	c.*1429A>T		3_prime_UTR_variant	3/3	1	NM_020638.3	P1

Frequencies

GnomAD3 genomes

AF:

0.228

AC:

34613

AN:

151746

Hom.:

4399

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.194

Gnomad NFE

AF:

0.273

Gnomad OTH

AF:

0.236

GnomAD4 exome

AF:

0.237

AC:

16580

AN:

70102

Hom.:

2075

Cov.:

AF XY:

0.235

AC XY:

7614

AN XY:

32370

show subpopulations

Gnomad4 AFR exome

AF:

0.109

Gnomad4 AMR exome

AF:

0.269

Gnomad4 ASJ exome

AF:

0.259

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.164

Gnomad4 FIN exome

AF:

0.292

Gnomad4 NFE exome

AF:

0.267

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.228

AC:

34613

AN:

151864

Hom.:

4401

Cov.:

AF XY:

0.230

AC XY:

17070

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.260

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.174

Gnomad4 FIN

AF:

0.335

Gnomad4 NFE

AF:

0.273

Gnomad4 OTH

AF:

0.233

Alfa

AF:

0.113

Hom.:

235

Bravo

AF:

0.219

Asia WGS

AF:

0.191

AC:

662

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 11, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal dominant hypophosphatemic rickets

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Tumoral calcinosis, hyperphosphatemic, familial, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.6

DANN

Benign

0.53

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