X-147912049-CGCG-C

Variant summary

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

The NM_002024.6(FMR1):c.-102_-100del 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 0.011 (4 hom., 67 hem., cov: 2)
  • Exomes 𝑓: 0.025 (2 hom. 36 hem.)
  • Failed GnomAD Quality Control
• Consequence: FMR1 NM_002024.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53

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-CGCG-C is Benign according to our data. Variant chrX-147912049-CGCG-C is described in ClinVar as [Benign]. Clinvar id is 766072.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0113 (397/35034) while in subpopulation EAS AF= 0.0194 (11/567). AF 95% confidence interval is 0.0145. There are 4 homozygotes in gnomad4. There are 67 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMR1	NM_002024.6	c.-102_-100del		5_prime_UTR_variant	1/17	ENST00000370475.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMR1	ENST00000370475.9	c.-102_-100del		5_prime_UTR_variant	1/17	1	NM_002024.6	P3

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 395 AN: 35036 Hom.: 4 Cov.: 2 AF XY: 0.0116 AC XY: 67 AN XY: 5794

Gnomad AFR AF: 0.00669

Gnomad AMI AF: 0.0114

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.00847

Gnomad EAS AF: 0.0194

Gnomad SAS AF: 0.0165

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0112

Gnomad OTH AF: 0.0129

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0254 AC: 150 AN: 5899 Hom.: 2 AF XY: 0.0117 AC XY: 36 AN XY: 3071

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.200

Gnomad4 ASJ exome AF: 0.0323

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.0625

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0253

Gnomad4 OTH exome AF: 0.0119

GnomAD4 genome AF: 0.0113 AC: 397 AN: 35034 Hom.: 4 Cov.: 2 AF XY: 0.0116 AC XY: 67 AN XY: 5798

Gnomad4 AFR AF: 0.00669

Gnomad4 AMR AF: 0.0185

Gnomad4 ASJ AF: 0.00847

Gnomad4 EAS AF: 0.0194

Gnomad4 SAS AF: 0.0189

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0112

Gnomad4 OTH AF: 0.0128

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

- -

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;