rs11063118

Positions:

• chr12-4372398-T-C
• chr12-4372398-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020638.3(FGF23):​c.315+196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,982 control chromosomes in the GnomAD database, including 3,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (3892 hom., cov: 31)
• Consequence: FGF23 NM_020638.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 12-4372398-T-C is Benign according to our data. Variant chr12-4372398-T-C is described in ClinVar as [Benign]. Clinvar id is 1259786.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF23	NM_020638.3	c.315+196A>G		intron_variant		ENST00000237837.2	NP_065689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF23	ENST00000237837.2	c.315+196A>G		intron_variant		1	NM_020638.3	ENSP00000237837	P1
FGF23	ENST00000648269.1	n.1815+196A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33034 AN: 151866 Hom.: 3885 Cov.: 31

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.247

Gnomad SAS AF: 0.342

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.217

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.217 AC: 33055 AN: 151982 Hom.: 3892 Cov.: 31 AF XY: 0.220 AC XY: 16321 AN XY: 74252

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.272

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.343

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.214

Alfa AF: 0.211 Hom.: 1416

Bravo AF: 0.210

Asia WGS AF: 0.280 AC: 977 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.6
DANN	Benign	0.64

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

Other links and lift over

dbSNP: rs11063118; hg19: chr12-4481564;