X-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

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

The NM_002024.6(FMR1):c.-129_-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 0.020 (10 hom., 114 hem., cov: 2)
  • Exomes 𝑓: 0.00047 (0 hom. 1 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-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 761197.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0198 (694/35017) while in subpopulation EAS AF= 0.0511 (29/567). AF 95% confidence interval is 0.0366. There are 10 homozygotes in gnomad4. There are 114 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 10 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMR1	NM_002024.6	c.-129_-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.-129_-100dup		5_prime_UTR_variant	1/17	1	NM_002024.6	P3

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 693 AN: 35019 Hom.: 10 Cov.: 2 AF XY: 0.0195 AC XY: 113 AN XY: 5795

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.0226

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0122

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.00240

Gnomad MID AF: 0.0580

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0237

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000474 AC: 3 AN: 6328 Hom.: 0 Cov.: 0 AF XY: 0.000293 AC XY: 1 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: 0.000337

Gnomad4 OTH exome AF: 0.00578

GnomAD4 genome AF: 0.0198 AC: 694 AN: 35017 Hom.: 10 Cov.: 2 AF XY: 0.0197 AC XY: 114 AN XY: 5799

Gnomad4 AFR AF: 0.0288

Gnomad4 AMR AF: 0.0218

Gnomad4 ASJ AF: 0.0122

Gnomad4 EAS AF: 0.0511

Gnomad4 SAS AF: 0.0235

Gnomad4 FIN AF: 0.00240

Gnomad4 NFE AF: 0.0148

Gnomad4 OTH AF: 0.0236

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;