X-147912049-C-CGCGGCGGCGGCGGCG

Position:

• chrX-147912049-C-CGCGGCGGCGGCGGCG

Variant summary

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

The NM_002024.6(FMR1):​c.-114_-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 0.0078 (4 hom., 41 hem., cov: 2)
  • Exomes 𝑓: 0.00016 (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-CGCGGCGGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 793052.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00776 (273/35164) while in subpopulation AMR AF= 0.00978 (27/2762). AF 95% confidence interval is 0.00725. There are 4 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMR1	NM_002024.6	c.-114_-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.-114_-100dup		5_prime_UTR_variant	1/17	1	NM_002024.6	P3

Frequencies

GnomAD3 genomes AF: 0.00776 AC: 273 AN: 35166 Hom.: 4 Cov.: 2 AF XY: 0.00707 AC XY: 41 AN XY: 5800

Gnomad AFR AF: 0.00637

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00980

Gnomad ASJ AF: 0.00481

Gnomad EAS AF: 0.00528

Gnomad SAS AF: 0.00469

Gnomad FIN AF: 0.00718

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00829

Gnomad OTH AF: 0.0194

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000158 AC: 1 AN: 6324 Hom.: 0 Cov.: 0 AF XY: 0.000293 AC XY: 1 AN XY: 3414

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: 0.000169

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00776 AC: 273 AN: 35164 Hom.: 4 Cov.: 2 AF XY: 0.00706 AC XY: 41 AN XY: 5804

Gnomad4 AFR AF: 0.00636

Gnomad4 AMR AF: 0.00978

Gnomad4 ASJ AF: 0.00481

Gnomad4 EAS AF: 0.00528

Gnomad4 SAS AF: 0.00471

Gnomad4 FIN AF: 0.00718

Gnomad4 NFE AF: 0.00829

Gnomad4 OTH AF: 0.0193

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

- -

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;