NM_002024.6:c.-117_-100delCGGCGGCGGCGGCGGCGG

Variant names:

• chrX-147912049-CGCGGCGGCGGCGGCGGCG-C
• rs193922936
• NM_002024.6:c.-117_-100delCGGCGGCGGCGGCGGCGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_002024.6(FMR1):​c.-117_-100delCGGCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000632 in 6,326 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 2)
  • Exomes 𝑓: 0.00063 (0 hom. 2 hem.)
• Consequence: FMR1 NM_002024.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• Publications: 0 publications found

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-AS1 (HGNC:39081): (FMR1 antisense RNA 1)

ENSG00000274086 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000632 (4/6326) while in subpopulation NFE AF = 0.000674 (4/5933). AF 95% confidence interval is 0.00023. There are 0 homozygotes in GnomAdExome4. There are 2 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.
• BS2: High Hemizygotes in GnomAdExome4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6	c.-117_-100delCGGCGGCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.-117_-100delCGGCGGCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes Cov.: 2

GnomAD4 exome AF: 0.000632 AC: 4 AN: 6326 Hom.: 0 AF XY: 0.000585 AC XY: 2 AN XY: 3416

African (AFR) AF: 0.00 AC: 0 AN: 33

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 33

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 97

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3

European-Non Finnish (NFE) AF: 0.000674 AC: 4 AN: 5933

Other (OTH) AF: 0.00 AC: 0 AN: 173

GnomAD4 genome Cov.: 2

Alfa AF: 0.00 Hom.: 89

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

Other links and lift over

dbSNP: rs193922936; hg19: chrX-146993567;