rs1805576

Variant names:

• chr3-180949777-C-G
• rs1805576
• NM_005087.4:c.630+434C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-180949777-C-G
• chr3-180949777-C-T

Variant summary

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

The NM_005087.4(FXR1):​c.630+434C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,098 control chromosomes in the GnomAD database, including 4,564 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 (4564 hom., cov: 33)
• Consequence: FXR1 NM_005087.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.411
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.307 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR1	NM_005087.4	MANE Select	c.630+434C>G		intron	N/A	NP_005078.2	P51114-1
	FXR1	NM_001441509.1		c.630+434C>G		intron	N/A	NP_001428438.1
	FXR1	NM_001441510.1		c.630+434C>G		intron	N/A	NP_001428439.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FXR1	ENST00000357559.9	TSL:1 MANE Select	c.630+434C>G		intron	N/A	ENSP00000350170.3	P51114-1
	FXR1	ENST00000445140.6	TSL:1	c.630+434C>G		intron	N/A	ENSP00000388828.2	P51114-2
	FXR1	ENST00000963215.1		c.630+434C>G		intron	N/A	ENSP00000633274.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36345 AN: 151980 Hom.: 4539 Cov.: 33

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.239 AC: 36412 AN: 152098 Hom.: 4564 Cov.: 33 AF XY: 0.234 AC XY: 17429 AN XY: 74366

African (AFR) AF: 0.311 AC: 12895 AN: 41430

American (AMR) AF: 0.205 AC: 3135 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1025 AN: 3468

East Asian (EAS) AF: 0.146 AC: 756 AN: 5178

South Asian (SAS) AF: 0.230 AC: 1109 AN: 4828

European-Finnish (FIN) AF: 0.156 AC: 1648 AN: 10594

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

European-Non Finnish (NFE) AF: 0.220 AC: 14947 AN: 67988

Other (OTH) AF: 0.268 AC: 565 AN: 2112

Alfa AF: 0.105 Hom.: 149

Bravo AF: 0.246

Asia WGS AF: 0.248 AC: 861 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.59
PhyloP100		-0.41
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: rs1805576; hg19: chr3-180667565;