rs28900

Positions:

• chrX-147912583-C-A
• chrX-147912583-C-G

Variant summary

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

The NM_002024.6(FMR1):​c.51+353C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0974 in 303,910 control chromosomes in the GnomAD database, including 2,647 homozygotes. There are 9,519 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 0.078 (650 hom., 2806 hem., cov: 24)
  • Exomes 𝑓: 0.11 (1997 hom. 6713 hem.)
• Consequence: FMR1 NM_002024.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

Genes affected

FMR1 (HGNC:3775): (fragile X messenger ribonucleoprotein 1) The protein encoded by this gene binds RNA and is associated with polysomes. The encoded protein may be involved in mRNA trafficking from the nucleus to the cytoplasm. A trinucleotide repeat (CGG) in the 5' UTR is normally found at 6-53 copies, but an expansion to 55-230 repeats is the cause of fragile X syndrome. Expansion of the trinucleotide repeat may also cause one form of premature ovarian failure (POF1). Multiple alternatively spliced transcript variants that encode different protein isoforms and which are located in different cellular locations have been described for this gene. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMR1	NM_002024.6	c.51+353C>A		intron_variant		ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.51+353C>A		intron_variant		1	NM_002024.6	ENSP00000359506	P3

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 8761 AN: 112520 Hom.: 652 Cov.: 24 AF XY: 0.0806 AC XY: 2798 AN XY: 34704

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.0538

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0505

Gnomad MID AF: 0.0504

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.109 AC: 20821 AN: 191332 Hom.: 1997 AF XY: 0.108 AC XY: 6713 AN XY: 61962

Gnomad4 AFR exome AF: 0.0214

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.0473

Gnomad4 EAS exome AF: 0.501

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0579

Gnomad4 NFE exome AF: 0.0582

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0779 AC: 8769 AN: 112578 Hom.: 650 Cov.: 24 AF XY: 0.0807 AC XY: 2806 AN XY: 34772

Gnomad4 AFR AF: 0.0204

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.0538

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0505

Gnomad4 NFE AF: 0.0538

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0694 Hom.: 3275

Bravo AF: 0.0967

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	8.8
DANN	Benign	0.82

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: rs28900; hg19: chrX-146994101;