X-147912049-C-CGCGGCG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002024.6(FMR1):c.-105_-100dup 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 0.043 (28 hom., 326 hem., cov: 2)
  • Exomes 𝑓: 0.020 (4 hom. 82 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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-147912049-C-CGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCG is described in ClinVar as [Benign]. Clinvar id is 794273.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMR1	NM_002024.6	c.-105_-100dup		5_prime_UTR_variant	1/17	ENST00000370475.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMR1	ENST00000370475.9	c.-105_-100dup		5_prime_UTR_variant	1/17	1	NM_002024.6	P3

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 1514 AN: 35122 Hom.: 28 Cov.: 2 AF XY: 0.0561 AC XY: 325 AN XY: 5798

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0337

Gnomad ASJ AF: 0.0228

Gnomad EAS AF: 0.0105

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0258

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0199 AC: 124 AN: 6223 Hom.: 4 Cov.: 0 AF XY: 0.0247 AC XY: 82 AN XY: 3323

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0201

Gnomad4 OTH exome AF: 0.0289

GnomAD4 genome AF: 0.0430 AC: 1511 AN: 35120 Hom.: 28 Cov.: 2 AF XY: 0.0562 AC XY: 326 AN XY: 5802

Gnomad4 AFR AF: 0.0310

Gnomad4 AMR AF: 0.0336

Gnomad4 ASJ AF: 0.0228

Gnomad4 EAS AF: 0.0105

Gnomad4 SAS AF: 0.0188

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0530

Gnomad4 OTH AF: 0.0257

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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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;