X-147912049-CGCGGCGGCGGCGGCGGCGGCG-CGCGGCG

Variant names:

• chrX-147912049-CGCGGCGGCGGCGGCG-C
• rs193922936
• NM_002024.6:c.-114_-100delCGGCGGCGGCGGCGG

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_002024.6(FMR1):​c.-114_-100delCGGCGGCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 41,495 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00014 (0 hom., 1 hem., cov: 2)
  • Exomes 𝑓: 0.00047 (0 hom. 0 hem.)
• Consequence: FMR1 NM_002024.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.66
• Publications: 0 publications found

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-AS1 (HGNC:39081): (FMR1 antisense RNA 1)

ENSG00000274086 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant X-147912049-CGCGGCGGCGGCGGCG-C is Benign according to our data. Variant chrX-147912049-CGCGGCGGCGGCGGCG-C is described in ClinVar as Benign. ClinVar VariationId is 1168103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000474 (3/6323) while in subpopulation NFE AF = 0.000506 (3/5931). AF 95% confidence interval is 0.000137. There are 0 homozygotes in GnomAdExome4. There are 0 alleles in the male GnomAdExome4 subpopulation. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6	c.-114_-100delCGGCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.-114_-100delCGGCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes AF: 0.000142 AC: 5 AN: 35172 Hom.: 0 Cov.: 2

Gnomad AFR AF: 0.000103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00120

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000155

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000474 AC: 3 AN: 6323 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 3413

African (AFR) AF: 0.00 AC: 0 AN: 32

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 33

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 97

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3

European-Non Finnish (NFE) AF: 0.000506 AC: 3 AN: 5931

Other (OTH) AF: 0.00 AC: 0 AN: 173

GnomAD4 genome AF: 0.000142 AC: 5 AN: 35172 Hom.: 0 Cov.: 2 AF XY: 0.000172 AC XY: 1 AN XY: 5800

African (AFR) AF: 0.000103 AC: 1 AN: 9740

American (AMR) AF: 0.00 AC: 0 AN: 2760

Ashkenazi Jewish (ASJ) AF: 0.00120 AC: 1 AN: 830

East Asian (EAS) AF: 0.00 AC: 0 AN: 569

South Asian (SAS) AF: 0.00 AC: 0 AN: 426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 69

European-Non Finnish (NFE) AF: 0.000155 AC: 3 AN: 19298

Other (OTH) AF: 0.00 AC: 0 AN: 465

Alfa AF: 0.00 Hom.: 89

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 16, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs193922936; hg19: chrX-146993567;