X-147912049-C-CGCG

Position:

• chrX-147912049-C-CGCG

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_-100dupCGG 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 0.019 (9 hom., 126 hem., cov: 2)
  • Exomes 𝑓: 0.0049 (0 hom. 21 hem.)
• 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]

FMR1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant X-147912049-C-CGCG is Benign according to our data. Variant chrX-147912049-C-CGCG is described in ClinVar as [Benign]. Clinvar id is 752727.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0194 (680/35117) while in subpopulation AMR AF= 0.0297 (82/2763). AF 95% confidence interval is 0.0245. There are 9 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FMR1	NM_002024.6	c.-102_-100dupCGG		5_prime_UTR_variant	1/17	ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475	c.-102_-100dupCGG		5_prime_UTR_variant	1/17	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 680 AN: 35119 Hom.: 9 Cov.: 2 AF XY: 0.0216 AC XY: 125 AN XY: 5797

Gnomad AFR AF: 0.0177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.00879

Gnomad SAS AF: 0.0188

Gnomad FIN AF: 0.00120

Gnomad MID AF: 0.0290

Gnomad NFE AF: 0.0197

Gnomad OTH AF: 0.0151

GnomAD4 exome AF: 0.00493 AC: 31 AN: 6283 Hom.: 0 Cov.: 0 AF XY: 0.00622 AC XY: 21 AN XY: 3377

Gnomad4 AFR exome AF: 0.0606

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: 0.00475

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0194 AC: 680 AN: 35117 Hom.: 9 Cov.: 2 AF XY: 0.0217 AC XY: 126 AN XY: 5801

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.0297

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.00879

Gnomad4 SAS AF: 0.0188

Gnomad4 FIN AF: 0.00120

Gnomad4 NFE AF: 0.0197

Gnomad4 OTH AF: 0.0150

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;