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

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002024.6(FMR1):​c.-117_-100dupCGGCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0067 (3 hom., 39 hem., cov: 2)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: FMR1 NM_002024.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.618

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-147912049-C-CGCGGCGGCGGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCGGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 763160.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00671 (236/35167) while in subpopulation NFE AF= 0.00824 (159/19289). AF 95% confidence interval is 0.0072. There are 3 homozygotes in gnomad4. There are 39 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00671 AC: 236 AN: 35169 Hom.: 3 Cov.: 2 AF XY: 0.00673 AC XY: 39 AN XY: 5799

Gnomad AFR AF: 0.00544

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00435

Gnomad ASJ AF: 0.00120

Gnomad EAS AF: 0.00703

Gnomad SAS AF: 0.00469

Gnomad FIN AF: 0.00239

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00824

Gnomad OTH AF: 0.00645

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 6328 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00671 AC: 236 AN: 35167 Hom.: 3 Cov.: 2 AF XY: 0.00672 AC XY: 39 AN XY: 5803

Gnomad4 AFR AF: 0.00544

Gnomad4 AMR AF: 0.00434

Gnomad4 ASJ AF: 0.00120

Gnomad4 EAS AF: 0.00703

Gnomad4 SAS AF: 0.00471

Gnomad4 FIN AF: 0.00239

Gnomad4 NFE AF: 0.00824

Gnomad4 OTH AF: 0.00642

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs193922936; hg19: chrX-146993567;