3-180933327-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_005087.4(FXR1):c.52-7C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 1,524,420 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 6 hom. )

Consequence

FXR1
NM_005087.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005346

Clinical Significance

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

Conservation

PhyloP100: -1.18

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 3-180933327-C-T is Benign according to our data. Variant chr3-180933327-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 729241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
FXR1	NM_005087.4 linkuse as main transcript	c.52-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000357559.9
FXR1	NM_001013438.3 linkuse as main transcript	c.52-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
FXR1	NM_001013439.3 linkuse as main transcript	c.-204-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
FXR1	NM_001363882.1 linkuse as main transcript	c.-204-7C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FXR1	ENST00000357559.9 linkuse as main transcript	c.52-7C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_005087.4		P51114-1

Frequencies

GnomAD3 genomes

AF:

0.00239

AC:

364

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000990

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00386

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00347

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00198

AC:

494

AN:

249766

Hom.:

AF XY:

0.00204

AC XY:

275

AN XY:

134976

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.00269

Gnomad ASJ exome

AF:

0.00348

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000200

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00295

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00241

AC:

3309

AN:

1372152

Hom.:

Cov.:

AF XY:

0.00239

AC XY:

1642

AN XY:

687788

show subpopulations

Gnomad4 AFR exome

AF:

0.000822

Gnomad4 AMR exome

AF:

0.00287

Gnomad4 ASJ exome

AF:

0.00341

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.000155

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00276

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152268

Hom.:

Cov.:

AF XY:

0.00212

AC XY:

158

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000987

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00347

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.00257

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00360

EpiControl

AF:

0.00320

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2024	FXR1: BP4, BS2 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jun 08, 2018	- -

Myopathy, congenital, with respiratory insufficiency and bone fractures;C5394193:Myopathy, congenital proximal, with minicore lesions

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

May 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

Cadd

Benign

6.9

Dann

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000053

dbscSNV1_RF

Benign

0.036

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