chrX-147912049-C-CGCGGCGGCG

Variant names:

• chrX-147912049-C-CGCGGCGGCG
• rs193922936
• NM_002024.6:c.-108_-100dupCGGCGGCGG

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002024.6(FMR1):​c.-108_-100dupCGGCGGCGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (118 hom., 774 hem., cov: 2)
  • Exomes 𝑓: 0.045 (9 hom. 186 hem.)
  • Failed GnomAD Quality Control
• Consequence: FMR1 NM_002024.6 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.618
• 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 -16 ACMG points.

• BP6: Variant X-147912049-C-CGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCG is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 763962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002024.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMR1	NM_002024.6	MANE Select	c.-108_-100dupCGGCGGCGG		5_prime_UTR	Exon 1 of 17	NP_002015.1
	FMR1	NM_001185076.2		c.-108_-100dupCGGCGGCGG		5_prime_UTR	Exon 1 of 16	NP_001172005.1
	FMR1	NM_001185082.2		c.-108_-100dupCGGCGGCGG		5_prime_UTR	Exon 1 of 16	NP_001172011.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMR1	ENST00000370475.9	TSL:1 MANE Select	c.-108_-100dupCGGCGGCGG		5_prime_UTR	Exon 1 of 17	ENSP00000359506.5
	FMR1	ENST00000218200.12	TSL:1	c.-108_-100dupCGGCGGCGG		5_prime_UTR	Exon 1 of 16	ENSP00000218200.8
	FMR1	ENST00000439526.6	TSL:1	c.-108_-100dupCGGCGGCGG		5_prime_UTR	Exon 1 of 16	ENSP00000395923.2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 3603 AN: 35043 Hom.: 117 Cov.: 2

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.0447

Gnomad AMR AF: 0.0693

Gnomad ASJ AF: 0.0778

Gnomad EAS AF: 0.0141

Gnomad SAS AF: 0.0728

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0580

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.0989

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0452 AC: 281 AN: 6216 Hom.: 9 Cov.: 0 AF XY: 0.0561 AC XY: 186 AN XY: 3316

African (AFR) AF: 0.0303 AC: 1 AN: 33

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

Ashkenazi Jewish (ASJ) AF: 0.0313 AC: 1 AN: 32

East Asian (EAS) AF: 0.167 AC: 1 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: 0.0455 AC: 265 AN: 5827

Other (OTH) AF: 0.0765 AC: 13 AN: 170

GnomAD4 genome AF: 0.103 AC: 3605 AN: 35041 Hom.: 118 Cov.: 2 AF XY: 0.134 AC XY: 774 AN XY: 5795

African (AFR) AF: 0.0427 AC: 416 AN: 9734

American (AMR) AF: 0.0692 AC: 191 AN: 2762

Ashkenazi Jewish (ASJ) AF: 0.0778 AC: 64 AN: 823

East Asian (EAS) AF: 0.0141 AC: 8 AN: 569

South Asian (SAS) AF: 0.0729 AC: 31 AN: 425

European-Finnish (FIN) AF: 0.181 AC: 151 AN: 832

Middle Eastern (MID) AF: 0.0690 AC: 4 AN: 58

European-Non Finnish (NFE) AF: 0.140 AC: 2686 AN: 19192

Other (OTH) AF: 0.0985 AC: 46 AN: 467

Alfa AF: 0.0247 Hom.: 89

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.62
Mutation Taster		=265/35	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;