12-4368914-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant hypophosphatemic rickets
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
tumoral calcinosis, hyperphosphatemic, familial, 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
tumoral calcinosis, hyperphosphatemic, familial, 1
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

FGF23 links:

ENSG00000285901 (HGNC:):

ENSG00000285901 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FGF23	NM_020638.3 link	c.*1429A>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000237837.2	NP_065689.1	Q9GZV9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FGF23	ENST00000237837.2 link	c.*1429A>T	3_prime_UTR_variant	Exon 3 of 3	1	NM_020638.3	ENSP00000237837.1	Q9GZV9
ENSG00000285901	ENST00000674624.1 link	n.*1204+2632T>A	intron_variant	Intron 9 of 9			ENSP00000501898.1	A0A6Q8PFP0
ENSG00000285901	ENST00000648100.1 link	n.*1967+2632T>A	intron_variant	Intron 11 of 11			ENSP00000497536.1	A0A3B3IT44

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

African (AFR)

AF:

0.109

AC:

363

AN:

3334

American (AMR)

AF:

0.269

AC:

575

AN:

2140

Ashkenazi Jewish (ASJ)

AF:

0.259

AC:

1159

AN:

4478

East Asian (EAS)

AF:

0.132

AC:

1319

AN:

10026

South Asian (SAS)

AF:

0.164

AC:

AN:

598

European-Finnish (FIN)

AF:

0.292

AC:

AN:

Middle Eastern (MID)

AF:

0.222

AC:

AN:

428

European-Non Finnish (NFE)

AF:

0.267

AC:

11523

AN:

43168

Other (OTH)

AF:

0.244

AC:

1434

AN:

5882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

647

1294

1941

2588

3235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.228

AC:

34613

AN:

151864

Hom.:

4401

Cov.:

AF XY:

0.230

AC XY:

17070

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.110

AC:

4540

AN:

41404

American (AMR)

AF:

0.287

AC:

4381

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

900

AN:

3464

East Asian (EAS)

AF:

0.205

AC:

1062

AN:

5170

South Asian (SAS)

AF:

0.174

AC:

836

AN:

4810

European-Finnish (FIN)

AF:

0.335

AC:

3513

AN:

10498

Middle Eastern (MID)

AF:

0.188

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.273

AC:

18536

AN:

67942

Other (OTH)

AF:

0.233

AC:

492

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1302

2604

3907

5209

6511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

May 11, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal dominant hypophosphatemic rickets

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.6

(source)

DANN

Benign

0.53

PhyloP100

0.30

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over