Genetic Variant FMR1:c.*1174C>T (chrX-147950018-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002024.6(FMR1):c.*1174C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 312,594 control chromosomes in the GnomAD database, including 13,110 homozygotes. There are 33,696 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.38 ( 6973 hom., 11510 hem., cov: 22)

Exomes 𝑓: 0.29 ( 6137 hom. 22186 hem. )

Consequence

FMR1
NM_002024.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.149

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant X-147950018-C-T is Benign according to our data. Variant chrX-147950018-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6 link	c.*1174C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000370475.9	NP_002015.1	Q06787-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9 link	c.*1174C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_002024.6	ENSP00000359506.5		Q06787-1

Frequencies

GnomAD3 genomes

AF:

0.375

AC:

40949

AN:

109143

Hom.:

6973

Cov.:

AF XY:

0.363

AC XY:

11480

AN XY:

31605

show subpopulations

Gnomad AFR

AF:

0.629

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.364

Gnomad ASJ

AF:

0.167

Gnomad EAS

AF:

0.706

Gnomad SAS

AF:

0.277

Gnomad FIN

AF:

0.235

Gnomad MID

AF:

0.321

Gnomad NFE

AF:

0.240

Gnomad OTH

AF:

0.397

GnomAD3 exomes

AF:

0.326

AC:

28129

AN:

86159

Hom.:

3954

AF XY:

0.308

AC XY:

9052

AN XY:

29425

show subpopulations

Gnomad AFR exome

AF:

0.643

Gnomad AMR exome

AF:

0.355

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.719

Gnomad SAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.285

AC:

58029

AN:

203408

Hom.:

6137

Cov.:

AF XY:

0.278

AC XY:

22186

AN XY:

79698

show subpopulations

Gnomad4 AFR exome

AF:

0.636

Gnomad4 AMR exome

AF:

0.356

Gnomad4 ASJ exome

AF:

0.171

Gnomad4 EAS exome

AF:

0.708

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.251

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.310

GnomAD4 genome

AF:

0.375

AC:

40976

AN:

109186

Hom.:

6973

Cov.:

AF XY:

0.364

AC XY:

11510

AN XY:

31658

show subpopulations

Gnomad4 AFR

AF:

0.629

Gnomad4 AMR

AF:

0.364

Gnomad4 ASJ

AF:

0.167

Gnomad4 EAS

AF:

0.705

Gnomad4 SAS

AF:

0.275

Gnomad4 FIN

AF:

0.235

Gnomad4 NFE

AF:

0.240

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.262

Hom.:

10971

Bravo

AF:

0.407

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.23

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over