chrX-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCG

Position:

• chrX-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

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

The NM_002024.6(FMR1):​c.-126_-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 0.017 (12 hom., 110 hem., cov: 2)
  • Exomes 𝑓: 0.00032 (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-CGCGGCGGCGGCGGCGGCGGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 762791.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0174 (610/35114) while in subpopulation EAS AF= 0.051 (29/569). AF 95% confidence interval is 0.0365. There are 12 homozygotes in gnomad4. There are 110 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMR1	NM_002024.6	c.-126_-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.-126_-100dup		5_prime_UTR_variant	1/17	1	NM_002024.6	P3

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 610 AN: 35116 Hom.: 12 Cov.: 2 AF XY: 0.0190 AC XY: 110 AN XY: 5800

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0138

Gnomad ASJ AF: 0.0217

Gnomad EAS AF: 0.0510

Gnomad SAS AF: 0.0235

Gnomad FIN AF: 0.00120

Gnomad MID AF: 0.0145

Gnomad NFE AF: 0.00710

Gnomad OTH AF: 0.0258

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000316 AC: 2 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: 0.00

GnomAD4 genome AF: 0.0174 AC: 610 AN: 35114 Hom.: 12 Cov.: 2 AF XY: 0.0190 AC XY: 110 AN XY: 5804

Gnomad4 AFR AF: 0.0375

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.0217

Gnomad4 EAS AF: 0.0510

Gnomad4 SAS AF: 0.0235

Gnomad4 FIN AF: 0.00120

Gnomad4 NFE AF: 0.00710

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

Labcorp Genetics (formerly Invitae), Labcorp

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;