Genetic Variant NM_002024.6:c.-111_-100dupCGGCGGCGGCGG (chrX-147912049-C-CGCGGCGGCGGCG) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_002024.6(FMR1):c.-111_-100dupCGGCGGCGGCGG 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 0.027 ( 23 hom., 216 hem., cov: 2)

Exomes 𝑓: 0.0054 ( 0 hom. 24 hem. )

Failed GnomAD Quality Control

Consequence

FMR1
NM_002024.6 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.618

Variant links:

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 links:

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

FMR1-AS1 links:

ENSG00000274086 (HGNC:):

ENSG00000274086 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant X-147912049-C-CGCGGCGGCGGCG is Benign according to our data. Variant chrX-147912049-C-CGCGGCGGCGGCG is described in ClinVar as [Benign]. Clinvar id is 762804.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0271 (952/35152) while in subpopulation SAS AF= 0.0565 (24/425). AF 95% confidence interval is 0.0389. There are 23 homozygotes in gnomad4. There are 216 alleles in male gnomad4 subpopulation. Median coverage is 2. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6 link	c.-111_-100dupCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	ENST00000370475.9	NP_002015.1	Q06787-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475 link	c.-111_-100dupCGGCGGCGGCGG		5_prime_UTR_variant	Exon 1 of 17	1	NM_002024.6	ENSP00000359506.5		Q06787-1

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

953

AN:

35154

Hom.:

Cov.:

AF XY:

0.0374

AC XY:

217

AN XY:

5800

show subpopulations

Gnomad AFR

AF:

0.0215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0402

Gnomad ASJ

AF:

0.0867

Gnomad EAS

AF:

0.0123

Gnomad SAS

AF:

0.0563

Gnomad FIN

AF:

0.0144

Gnomad MID

AF:

0.0145

Gnomad NFE

AF:

0.0263

Gnomad OTH

AF:

0.0216

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00538

AC:

AN:

6319

Hom.:

Cov.:

AF XY:

0.00704

AC XY:

AN XY:

3409

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0303

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0206

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00523

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0271

AC:

952

AN:

35152

Hom.:

Cov.:

AF XY:

0.0372

AC XY:

216

AN XY:

5804

show subpopulations

Gnomad4 AFR

AF:

0.0214

Gnomad4 AMR

AF:

0.0402

Gnomad4 ASJ

AF:

0.0867

Gnomad4 EAS

AF:

0.0123

Gnomad4 SAS

AF:

0.0565

Gnomad4 FIN

AF:

0.0144

Gnomad4 NFE

AF:

0.0263

Gnomad4 OTH

AF:

0.0215

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over