3-180948154-G-A

Position:

• chr3-180948154-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXR1	NM_005087.4	c.271-193G>A		intron_variant		ENST00000357559.9	NP_005078.2
FXR1	NM_001013438.3	c.271-193G>A		intron_variant			NP_001013456.1
FXR1	NM_001013439.3	c.16-193G>A		intron_variant			NP_001013457.1
FXR1	NM_001363882.1	c.16-193G>A		intron_variant			NP_001350811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXR1	ENST00000357559.9	c.271-193G>A		intron_variant		1	NM_005087.4	ENSP00000350170.3

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

Gnomad4 AFR exome AF: 0.300

Gnomad4 AMR exome AF: 0.187

Gnomad4 ASJ exome AF: 0.303

Gnomad4 EAS exome AF: 0.0960

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.236

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

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.295

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.266

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.8
DANN	Benign	0.80

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

Other links and lift over

dbSNP: rs1805599; hg19: chr3-180665942;