Variant 3-180951420-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005087.4(FXR1):c.753C>T(p.Thr251Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00811 in 1,612,652 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 16 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 90 hom. )

Consequence

FXR1
NM_005087.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.76

Variant links:

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 links:

FXR1 (HGNC:):

FXR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 3-180951420-C-T is Benign according to our data. Variant chr3-180951420-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 777377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.76 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FXR1	NM_005087.4 linkuse as main transcript	c.753C>T	p.Thr251Thr	synonymous_variant	8/17	ENST00000357559.9	NP_005078.2	P51114-1
FXR1	NM_001013438.3 linkuse as main transcript	c.753C>T	p.Thr251Thr	synonymous_variant	8/16		NP_001013456.1	P51114-2
FXR1	NM_001013439.3 linkuse as main transcript	c.498C>T	p.Thr166Thr	synonymous_variant	9/18		NP_001013457.1	P51114-3
FXR1	NM_001363882.1 linkuse as main transcript	c.498C>T	p.Thr166Thr	synonymous_variant	9/17		NP_001350811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FXR1	ENST00000357559.9 linkuse as main transcript	c.753C>T	p.Thr251Thr	synonymous_variant	8/17	1	NM_005087.4	ENSP00000350170.3		P51114-1

Frequencies

GnomAD3 genomes

AF:

0.00850

AC:

1292

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0491

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00910

Gnomad OTH

AF:

0.00767

GnomAD3 exomes

AF:

0.00868

AC:

2180

AN:

251180

Hom.:

AF XY:

0.00862

AC XY:

1170

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00113

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00399

Gnomad FIN exome

AF:

0.0420

Gnomad NFE exome

AF:

0.00884

Gnomad OTH exome

AF:

0.00865

GnomAD4 exome

AF:

0.00807

AC:

11783

AN:

1460498

Hom.:

Cov.:

AF XY:

0.00800

AC XY:

5814

AN XY:

726702

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00159

Gnomad4 ASJ exome

AF:

0.00314

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00440

Gnomad4 FIN exome

AF:

0.0387

Gnomad4 NFE exome

AF:

0.00787

Gnomad4 OTH exome

AF:

0.00625

GnomAD4 genome

AF:

0.00849

AC:

1292

AN:

152154

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

746

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00412

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.0491

Gnomad4 NFE

AF:

0.00910

Gnomad4 OTH

AF:

0.00759

Alfa

AF:

0.00763

Hom.:

Bravo

AF:

0.00453

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00698

EpiControl

AF:

0.00545

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2024	FXR1: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 27, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.9

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over