chr3-180949777-C-G

Position:

• chr3-180949777-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXR1	NM_005087.4	c.630+434C>G		intron_variant		ENST00000357559.9	NP_005078.2
FXR1	NM_001013438.3	c.630+434C>G		intron_variant			NP_001013456.1
FXR1	NM_001013439.3	c.375+434C>G		intron_variant			NP_001013457.1
FXR1	NM_001363882.1	c.375+434C>G		intron_variant			NP_001350811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXR1	ENST00000357559.9	c.630+434C>G		intron_variant		1	NM_005087.4	ENSP00000350170

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

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.230

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.268

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.76
DANN	Benign	0.59

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: rs1805576; hg19: chr3-180667565;