rs591

Positions:

• chrX-138754725-C-A
• chrX-138754725-C-G
• chrX-138754725-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001139500.2(FGF13):​c.218-45797G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 110,148 control chromosomes in the GnomAD database, including 6,372 homozygotes. There are 11,545 hemizygotes in GnomAD. 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 0.37 (6372 hom., 11545 hem., cov: 22)
• Consequence: FGF13 NM_001139500.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258

Genes affected

FGF13 (HGNC:3670): (fibroblast growth factor 13) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth, and invasion. This gene is located in a region on chromosome X, which is associated with Borjeson-Forssman-Lehmann syndrome (BFLS), making it a possible candidate gene for familial cases of the BFLS, and for other syndromal and nonspecific forms of X-linked cognitive disability mapping to this region. Alternative splicing of this gene at the 5' end results in several transcript variants encoding different isoforms with different N-termini. [provided by RefSeq, Nov 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF13	NM_001139500.2	c.218-45797G>T		intron_variant			NP_001132972.1
FGF13	NM_001139501.2	c.131-45797G>T		intron_variant			NP_001132973.1
FGF13	NM_001139502.2	c.131-45797G>T		intron_variant			NP_001132974.1
FGF13	NM_001139498.2	c.50-45797G>T		intron_variant			NP_001132970.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF13	ENST00000436198.6	c.218-45797G>T		intron_variant		2		ENSP00000396198.2
FGF13	ENST00000441825.8	c.131-45797G>T		intron_variant		5		ENSP00000409276.2
FGF13	ENST00000455663.5	c.236-45797G>T		intron_variant		3		ENSP00000406916.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 40534 AN: 110093 Hom.: 6367 Cov.: 22 AF XY: 0.355 AC XY: 11505 AN XY: 32397

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.305

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.368 AC: 40585 AN: 110148 Hom.: 6372 Cov.: 22 AF XY: 0.356 AC XY: 11545 AN XY: 32462

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.334

Alfa AF: 0.325 Hom.: 2119

Bravo AF: 0.380

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.1
DANN	Benign	0.40

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs591; hg19: chrX-137836887;