rs29282

Variant names:

• chrX-147931085-T-C
• rs29282
• NM_002024.6:c.630+841T>C

Variant summary

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

The NM_002024.6(FMR1):​c.630+841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 111,445 control chromosomes in the GnomAD database, including 318 homozygotes. There are 2,544 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 0.082 (318 hom., 2543 hem., cov: 22)
  • Exomes 𝑓: 0.11 (0 hom. 1 hem.)
• Consequence: FMR1 NM_002024.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.097 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6	c.630+841T>C		intron_variant	Intron 7 of 16	ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.630+841T>C		intron_variant	Intron 7 of 16	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes AF: 0.0822 AC: 9156 AN: 111371 Hom.: 319 Cov.: 22 AF XY: 0.0756 AC XY: 2540 AN XY: 33611

Gnomad AFR AF: 0.0999

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0551

Gnomad ASJ AF: 0.0634

Gnomad EAS AF: 0.000841

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0936

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0846

Gnomad OTH AF: 0.0744

GnomAD4 exome AF: 0.111 AC: 2 AN: 18 Hom.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0822 AC: 9156 AN: 111427 Hom.: 318 Cov.: 22 AF XY: 0.0755 AC XY: 2543 AN XY: 33677

Gnomad4 AFR AF: 0.0999

Gnomad4 AMR AF: 0.0550

Gnomad4 ASJ AF: 0.0634

Gnomad4 EAS AF: 0.000844

Gnomad4 SAS AF: 0.0260

Gnomad4 FIN AF: 0.0936

Gnomad4 NFE AF: 0.0846

Gnomad4 OTH AF: 0.0735

Alfa AF: 0.0827 Hom.: 1018

Bravo AF: 0.0825

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.8
DANN	Benign	0.46

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: rs29282; hg19: chrX-147012604;