rs11063112

Variant names:

• chr12-4368914-T-A
• rs11063112
• NM_020638.3:c.*1429A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-4368914-T-A
• chr12-4368914-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.305
• Publications: 13 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: 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

ENSG00000285901 (HGNC:):

ACMG classification

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.

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.*1429A>T		3_prime_UTR	Exon 3 of 3	NP_065689.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF23	ENST00000237837.2	TSL:1 MANE Select	c.*1429A>T		3_prime_UTR	Exon 3 of 3	ENSP00000237837.1
	ENSG00000285901	ENST00000674624.1		n.*1204+2632T>A		intron	N/A	ENSP00000501898.1
	ENSG00000285901	ENST00000648100.1		n.*1967+2632T>A		intron	N/A	ENSP00000497536.1

Frequencies

GnomAD3 genomes AF: 0.228 AC: 34613 AN: 151746 Hom.: 4399 Cov.: 31

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.: 0 AF XY: 0.235 AC XY: 7614 AN XY: 32370

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: 98 AN: 598

European-Finnish (FIN) AF: 0.292 AC: 14 AN: 48

Middle Eastern (MID) AF: 0.222 AC: 95 AN: 428

European-Non Finnish (NFE) AF: 0.267 AC: 11523 AN: 43168

Other (OTH) AF: 0.244 AC: 1434 AN: 5882

GnomAD4 genome AF: 0.228 AC: 34613 AN: 151864 Hom.: 4401 Cov.: 31 AF XY: 0.230 AC XY: 17070 AN XY: 74194

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: 55 AN: 292

European-Non Finnish (NFE) AF: 0.273 AC: 18536 AN: 67942

Other (OTH) AF: 0.233 AC: 492 AN: 2108

Alfa AF: 0.113 Hom.: 235

Bravo AF: 0.219

Asia WGS AF: 0.191 AC: 662 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant hypophosphatemic rickets (1)
-	-	1	Tumoral calcinosis, hyperphosphatemic, familial, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.53
PhyloP100		0.30
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: rs11063112; hg19: chr12-4478080;