NM_005087.4:c.1604-2009G>A

Variant names:

• chr3-180973304-G-A
• rs1010471
• NM_005087.4:c.1604-2009G>A

Variant summary

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

The NM_005087.4(FXR1):​c.1604-2009G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 152,016 control chromosomes in the GnomAD database, including 21,461 homozygotes. 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 0.50 (21461 hom., cov: 33)
• Consequence: FXR1 NM_005087.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.02
• Publications: 6 publications found

Genes affected

FXR1 (HGNC:4023): (FMR1 autosomal homolog 1) The protein encoded by this gene is an RNA binding protein that interacts with the functionally-similar proteins FMR1 and FXR2. These proteins shuttle between the nucleus and cytoplasm and associate with polyribosomes, predominantly with the 60S ribosomal subunit. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

FXR1 Gene-Disease associations (from GenCC):

• congenital myopathy

  Inheritance: AR Classification: STRONG Submitted by: G2P
• myopathy, congenital, with respiratory insufficiency and bone fractures

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• myopathy, congenital proximal, with minicore lesions

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005087.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR1	NM_005087.4	MANE Select	c.1604-2009G>A		intron	N/A	NP_005078.2
	FXR1	NM_001441509.1		c.1772-2009G>A		intron	N/A	NP_001428438.1
	FXR1	NM_001441510.1		c.1691-2009G>A		intron	N/A	NP_001428439.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR1	ENST00000357559.9	TSL:1 MANE Select	c.1604-2009G>A		intron	N/A	ENSP00000350170.3
	FXR1	ENST00000445140.6	TSL:1	c.1604-2818G>A		intron	N/A	ENSP00000388828.2
	FXR1	ENST00000698794.1		c.1691-2009G>A		intron	N/A	ENSP00000513937.1

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75410 AN: 151900 Hom.: 21400 Cov.: 33

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.548

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.497 AC: 75531 AN: 152016 Hom.: 21461 Cov.: 33 AF XY: 0.492 AC XY: 36591 AN XY: 74302

African (AFR) AF: 0.792 AC: 32854 AN: 41494

American (AMR) AF: 0.446 AC: 6804 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1587 AN: 3470

East Asian (EAS) AF: 0.486 AC: 2508 AN: 5156

South Asian (SAS) AF: 0.548 AC: 2637 AN: 4816

European-Finnish (FIN) AF: 0.294 AC: 3098 AN: 10554

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.361 AC: 24549 AN: 67950

Other (OTH) AF: 0.499 AC: 1052 AN: 2110

Alfa AF: 0.403 Hom.: 6627

Bravo AF: 0.516

Asia WGS AF: 0.577 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0060
DANN	Benign	0.61
PhyloP100		-5.0
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: rs1010471; hg19: chr3-180691092;