X-147944810-ACC-AC

Variant names:

• chrX-147944810-AC-A
• rs11293471
• NM_002024.6:c.1472-56delC

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_002024.6(FMR1):​c.1472-56delC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in Lovd as Likely benign (no stars). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 1.0 (38552 hom., 25601 hem., cov: 0)
  • Exomes 𝑓: 1.0 (357435 hom. 337010 hem.)
  • Failed GnomAD Quality Control
• Consequence: FMR1 NM_002024.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233

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 Likely_benign. Variant got -1 ACMG points.

• BP6: Variant X-147944810-AC-A is Benign according to our data. Variant chrX-147944810-AC-A is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6	c.1472-56delC		intron_variant	Intron 14 of 16	ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.1472-56delC		intron_variant	Intron 14 of 16	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 102698 AN: 102703 Hom.: 38557 Cov.: 0 AF XY: 1.00 AC XY: 25579 AN XY: 25579 FAILED QC

Gnomad AFR AF: 1.00

Gnomad AMI AF: 1.00

Gnomad AMR AF: 1.00

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 1.00

Gnomad FIN AF: 0.999

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 1.00

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.999 AC: 1052801 AN: 1053725 Hom.: 357435 Cov.: 0 AF XY: 1.00 AC XY: 337010 AN XY: 337011

Gnomad4 AFR exome AF: 0.999

Gnomad4 AMR exome AF: 0.997

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 0.999

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.999

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 1.00 AC: 102710 AN: 102715 Hom.: 38552 Cov.: 0 AF XY: 1.00 AC XY: 25601 AN XY: 25601

Gnomad4 AFR AF: 1.00

Gnomad4 AMR AF: 1.00

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 1.00

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 1.00

Alfa AF: 0.999 Hom.: 8060

Asia WGS AF: 0.997 AC: 2430 AN: 2438

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
La Branchor		0.55
BranchPoint Hunter		4.0

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: rs11293471; hg19: chrX-147026330;