rs13312789

Variant names:

• chr12-4371878-G-A
• rs13312789
• NM_020638.3:c.315+716C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020638.3(FGF23):​c.315+716C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 151,992 control chromosomes in the GnomAD database, including 1,042 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.11 (1042 hom., cov: 30)
• Consequence: FGF23 NM_020638.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.118
• Publications: 6 publications found

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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• tumoral calcinosis, hyperphosphatemic, familial, 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
• tumoral calcinosis, hyperphosphatemic, familial, 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000285901 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020638.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF23	NM_020638.3	MANE Select	c.315+716C>T		intron	N/A	NP_065689.1	Q9GZV9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF23	ENST00000237837.2	TSL:1 MANE Select	c.315+716C>T		intron	N/A	ENSP00000237837.1	Q9GZV9
	ENSG00000285901	ENST00000674624.1		n.*1204+5596G>A		intron	N/A	ENSP00000501898.1	A0A6Q8PFP0
	ENSG00000285901	ENST00000648100.1		n.*1967+5596G>A		intron	N/A	ENSP00000497536.1	A0A3B3IT44

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16828 AN: 151874 Hom.: 1039 Cov.: 30

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.111 AC: 16838 AN: 151992 Hom.: 1042 Cov.: 30 AF XY: 0.113 AC XY: 8406 AN XY: 74304

African (AFR) AF: 0.0699 AC: 2899 AN: 41444

American (AMR) AF: 0.195 AC: 2983 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3468

East Asian (EAS) AF: 0.210 AC: 1083 AN: 5158

South Asian (SAS) AF: 0.113 AC: 543 AN: 4814

European-Finnish (FIN) AF: 0.126 AC: 1329 AN: 10550

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.110 AC: 7453 AN: 67970

Other (OTH) AF: 0.116 AC: 244 AN: 2112

Alfa AF: 0.106 Hom.: 618

Bravo AF: 0.114

Asia WGS AF: 0.164 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.0
DANN	Benign	0.50
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13312789; hg19: chr12-4481044;