X-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Position:

• chrX-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG

Variant summary

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

The NM_002024.6(FMR1):​c.-100_-99insCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGG 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 0.0012 (1 hom., 11 hem., cov: 2)
• 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-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 762636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00122 (43/35162) while in subpopulation AMR AF= 0.00253 (7/2765). AF 95% confidence interval is 0.00119. There are 1 homozygotes in gnomad4. There are 11 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd4 at 11 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMR1	NM_002024.6	c.-100_-99insCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR_variant	1/17	ENST00000370475.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMR1	ENST00000370475.9	c.-100_-99insCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGG		5_prime_UTR_variant	1/17	1	NM_002024.6	P3

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 43 AN: 35164 Hom.: 1 Cov.: 2 AF XY: 0.00190 AC XY: 11 AN XY: 5798

Gnomad AFR AF: 0.000513

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00254

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00176

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00120

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00145

Gnomad OTH AF: 0.00215

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00122 AC: 43 AN: 35162 Hom.: 1 Cov.: 2 AF XY: 0.00190 AC XY: 11 AN XY: 5802

Gnomad4 AFR AF: 0.000513

Gnomad4 AMR AF: 0.00253

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00176

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00120

Gnomad4 NFE AF: 0.00145

Gnomad4 OTH AF: 0.00214

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;