rs29285

Positions:

• chrX-147937967-T-G

Variant summary

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

The NM_002024.6(FMR1):​c.1126-132T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00813 in 572,818 control chromosomes in the GnomAD database, including 151 homozygotes. There are 1,218 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 0.026 (108 hom., 782 hem., cov: 23)
  • Exomes 𝑓: 0.0038 (43 hom. 436 hem.)
• Consequence: FMR1 NM_002024.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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]

FMR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMR1	NM_002024.6	c.1126-132T>G		intron_variant		ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.1126-132T>G		intron_variant		1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 2904 AN: 112094 Hom.: 108 Cov.: 23 AF XY: 0.0227 AC XY: 777 AN XY: 34250

Gnomad AFR AF: 0.0896

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00982

Gnomad ASJ AF: 0.000755

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000365

Gnomad FIN AF: 0.000327

Gnomad MID AF: 0.0125

Gnomad NFE AF: 0.000207

Gnomad OTH AF: 0.0186

GnomAD4 exome AF: 0.00380 AC: 1749 AN: 460671 Hom.: 43 AF XY: 0.00274 AC XY: 436 AN XY: 159069

Gnomad4 AFR exome AF: 0.0882

Gnomad4 AMR exome AF: 0.00605

Gnomad4 ASJ exome AF: 0.00124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000178

Gnomad4 FIN exome AF: 0.000774

Gnomad4 NFE exome AF: 0.000336

Gnomad4 OTH exome AF: 0.00847

GnomAD4 genome AF: 0.0259 AC: 2909 AN: 112147 Hom.: 108 Cov.: 23 AF XY: 0.0228 AC XY: 782 AN XY: 34313

Gnomad4 AFR AF: 0.0896

Gnomad4 AMR AF: 0.00980

Gnomad4 ASJ AF: 0.000755

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000367

Gnomad4 FIN AF: 0.000327

Gnomad4 NFE AF: 0.000207

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0000732 Hom.: 0

Bravo AF: 0.0304

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.0
DANN	Benign	0.49

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: rs29285; hg19: chrX-147019486;