NM_005087.4:c.271-193G>A

Variant names:

• chr3-180948154-G-A
• rs1805599
• NM_005087.4:c.271-193G>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.271-193G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 612,382 control chromosomes in the GnomAD database, including 15,229 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 0.24 (4486 hom., cov: 32)
  • Exomes 𝑓: 0.21 (10743 hom.)
• Consequence: FXR1 NM_005087.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.230
• Publications: 3 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=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 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.271-193G>A		intron	N/A	NP_005078.2
	FXR1	NM_001441509.1		c.271-193G>A		intron	N/A	NP_001428438.1
	FXR1	NM_001441510.1		c.271-193G>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.271-193G>A		intron	N/A	ENSP00000350170.3
	FXR1	ENST00000445140.6	TSL:1	c.271-193G>A		intron	N/A	ENSP00000388828.2
	FXR1	ENST00000963215.1		c.271-193G>A		intron	N/A	ENSP00000633274.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36127 AN: 152004 Hom.: 4464 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.210 AC: 96724 AN: 460258 Hom.: 10743 Cov.: 5 AF XY: 0.212 AC XY: 51495 AN XY: 242638

African (AFR) AF: 0.300 AC: 3729 AN: 12446

American (AMR) AF: 0.187 AC: 3183 AN: 17056

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 4106 AN: 13566

East Asian (EAS) AF: 0.0960 AC: 2971 AN: 30962

South Asian (SAS) AF: 0.227 AC: 9682 AN: 42596

European-Finnish (FIN) AF: 0.157 AC: 5791 AN: 36968

Middle Eastern (MID) AF: 0.256 AC: 520 AN: 2028

European-Non Finnish (NFE) AF: 0.217 AC: 60568 AN: 278486

Other (OTH) AF: 0.236 AC: 6174 AN: 26150

GnomAD4 genome AF: 0.238 AC: 36187 AN: 152124 Hom.: 4486 Cov.: 32 AF XY: 0.233 AC XY: 17322 AN XY: 74380

African (AFR) AF: 0.306 AC: 12698 AN: 41476

American (AMR) AF: 0.205 AC: 3130 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3466

East Asian (EAS) AF: 0.147 AC: 757 AN: 5166

South Asian (SAS) AF: 0.230 AC: 1110 AN: 4828

European-Finnish (FIN) AF: 0.156 AC: 1653 AN: 10596

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.220 AC: 14926 AN: 67986

Other (OTH) AF: 0.266 AC: 562 AN: 2116

Alfa AF: 0.124 Hom.: 192

Bravo AF: 0.245

Asia WGS AF: 0.245 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.8
DANN	Benign	0.80
PhyloP100		0.23
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: rs1805599; hg19: chr3-180665942;