Variant chr12-4372733-C-CG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020638.3(FGF23):c.212-37_212-36insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,345,846 control chromosomes in the GnomAD database, including 11,887 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.10 ( 960 hom., cov: 30)

Exomes 𝑓: 0.13 ( 10927 hom. )

Consequence

FGF23
NM_020638.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.23

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:

ENSG00000285901 (HGNC:):

ENSG00000285901 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 12-4372733-C-CG is Benign according to our data. Variant chr12-4372733-C-CG is described in ClinVar as [Benign]. Clinvar id is 1238224.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF23	NM_020638.3 linkuse as main transcript	c.212-37_212-36insC		intron_variant		ENST00000237837.2	NP_065689.1	Q9GZV9

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FGF23	ENST00000237837.2 linkuse as main transcript	c.212-37_212-36insC	intron_variant		1	NM_020638.3	ENSP00000237837.1	Q9GZV9
ENSG00000285901	ENST00000674624.1 linkuse as main transcript	n.1204+6451_1204+6452insG	intron_variant				ENSP00000501898.1	A0A6Q8PFP0
FGF23	ENST00000648269.1 linkuse as main transcript	n.1675_1676insC	non_coding_transcript_exon_variant	1/2
ENSG00000285901	ENST00000648100.1 linkuse as main transcript	n.1967+6451_1967+6452insG	intron_variant				ENSP00000497536.1	A0A3B3IT44

Frequencies

GnomAD3 genomes

AF:

0.102

AC:

15549

AN:

152070

Hom.:

957

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0500

Gnomad AMI

AF:

0.0855

Gnomad AMR

AF:

0.0759

Gnomad ASJ

AF:

0.0903

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.133

Gnomad OTH

AF:

0.0976

GnomAD3 exomes

AF:

0.121

AC:

30112

AN:

249886

Hom.:

2255

AF XY:

0.128

AC XY:

17344

AN XY:

135258

show subpopulations

Gnomad AFR exome

AF:

0.0498

Gnomad AMR exome

AF:

0.0589

Gnomad ASJ exome

AF:

0.0925

Gnomad EAS exome

AF:

0.0357

Gnomad SAS exome

AF:

0.218

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.128

AC:

152652

AN:

1193656

Hom.:

10927

Cov.:

AF XY:

0.131

AC XY:

79693

AN XY:

606838

show subpopulations

Gnomad4 AFR exome

AF:

0.0501

Gnomad4 AMR exome

AF:

0.0617

Gnomad4 ASJ exome

AF:

0.0910

Gnomad4 EAS exome

AF:

0.0421

Gnomad4 SAS exome

AF:

0.211

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.131

Gnomad4 OTH exome

AF:

0.115

GnomAD4 genome

AF:

0.102

AC:

15562

AN:

152190

Hom.:

960

Cov.:

AF XY:

0.102

AC XY:

7583

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0500

Gnomad4 AMR

AF:

0.0757

Gnomad4 ASJ

AF:

0.0903

Gnomad4 EAS

AF:

0.0338

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.132

Gnomad4 NFE

AF:

0.133

Gnomad4 OTH

AF:

0.0966

Alfa

AF:

0.120

Hom.:

263

Bravo

AF:

0.0924

Asia WGS

AF:

0.115

AC:

403

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

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