chrX-147912049-CGCGGCG-C

Variant names:

• chrX-147912049-CGCGGCG-C
• rs193922936
• NM_002024.6:c.-105_-100delCGGCGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_002024.6(FMR1):​c.-105_-100delCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000772 in 41,475 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00063 (0 hom., 6 hem., cov: 2)
  • Exomes 𝑓: 0.0016 (0 hom. 3 hem.)
• Consequence: FMR1 NM_002024.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.53
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant X-147912049-CGCGGCG-C is Benign according to our data. Variant chrX-147912049-CGCGGCG-C is described in ClinVar as Benign. ClinVar VariationId is 795779.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000626 (22/35167) while in subpopulation AMR AF = 0.00181 (5/2766). AF 95% confidence interval is 0.000712. There are 0 homozygotes in GnomAd4. There are 6 alleles in the male GnomAd4 subpopulation. Median coverage is 2. This position passed quality control check.
• BS2: High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6	c.-105_-100delCGGCGG		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.-105_-100delCGGCGG		5_prime_UTR_variant	Exon 1 of 17	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes AF: 0.000626 AC: 22 AN: 35169 Hom.: 0 Cov.: 2

Gnomad AFR AF: 0.000924

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00181

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00120

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000363

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 24 AF XY: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

GnomAD4 exome AF: 0.00159 AC: 10 AN: 6308 Hom.: 0 AF XY: 0.000882 AC XY: 3 AN XY: 3400

African (AFR) AF: 0.0313 AC: 1 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: 5

South Asian (SAS) AF: 0.00 AC: 0 AN: 94

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: 0.00152 AC: 9 AN: 5921

Other (OTH) AF: 0.00 AC: 0 AN: 172

GnomAD4 genome AF: 0.000626 AC: 22 AN: 35167 Hom.: 0 Cov.: 2 AF XY: 0.00103 AC XY: 6 AN XY: 5803

African (AFR) AF: 0.000924 AC: 9 AN: 9744

American (AMR) AF: 0.00181 AC: 5 AN: 2766

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 832

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 425

European-Finnish (FIN) AF: 0.00120 AC: 1 AN: 836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 58

European-Non Finnish (NFE) AF: 0.000363 AC: 7 AN: 19291

Other (OTH) AF: 0.00 AC: 0 AN: 467

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

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.5
Mutation Taster		=261/39	polymorphism

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;