rs971000

Variant names:

• chrX-147920275-A-G
• rs971000
• NM_002024.6:c.52-1658A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-147920275-A-G
• chrX-147920275-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002024.6(FMR1):​c.52-1658A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 110,438 control chromosomes in the GnomAD database, including 11,252 homozygotes. There are 16,211 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (11252 hom., 16211 hem., cov: 22)
• Consequence: FMR1 NM_002024.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158
• Publications: 5 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 Gene-Disease associations (from GenCC):

• fragile X syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
• fragile X-associated tremor/ataxia syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, Ambry Genetics
• premature ovarian failure 1

  Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• symptomatic form of fragile X syndrome in female carrier

  Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMR1	NM_002024.6	c.52-1658A>G		intron_variant	Intron 1 of 16	ENST00000370475.9	NP_002015.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMR1	ENST00000370475.9	c.52-1658A>G		intron_variant	Intron 1 of 16	1	NM_002024.6	ENSP00000359506.5

Frequencies

GnomAD3 genomes AF: 0.508 AC: 56034 AN: 110385 Hom.: 11255 Cov.: 22

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.460

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.512

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.508 AC: 56075 AN: 110438 Hom.: 11252 Cov.: 22 AF XY: 0.496 AC XY: 16211 AN XY: 32700

African (AFR) AF: 0.740 AC: 22409 AN: 30278

American (AMR) AF: 0.454 AC: 4728 AN: 10414

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 819 AN: 2623

East Asian (EAS) AF: 0.722 AC: 2505 AN: 3469

South Asian (SAS) AF: 0.444 AC: 1172 AN: 2638

European-Finnish (FIN) AF: 0.392 AC: 2304 AN: 5872

Middle Eastern (MID) AF: 0.453 AC: 97 AN: 214

European-Non Finnish (NFE) AF: 0.396 AC: 20924 AN: 52772

Other (OTH) AF: 0.513 AC: 767 AN: 1494

Alfa AF: 0.449 Hom.: 3564

Bravo AF: 0.531

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.64
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs971000; hg19: chrX-147001793;