Variant rs4647942 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004356.3(FGFRL1):c.60G>A(p.Pro20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 1,485,428 control chromosomes in the GnomAD database, including 169,384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 22012 hom., cov: 35)

Exomes 𝑓: 0.47 ( 147372 hom. )

Consequence

FGFRL1
NM_001004356.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.76

Variant links:

Genes affected

FGFRL1 (HGNC:3693): (fibroblast growth factor receptor like 1) The protein encoded by this gene is a member of the fibroblast growth factor receptor (FGFR) family, where amino acid sequence is highly conserved between members and throughout evolution. FGFR family members differ from one another in their ligand affinities and tissue distribution. A full-length representative protein would consist of an extracellular region, composed of three immunoglobulin-like domains, a single hydrophobic membrane-spanning segment and a cytoplasmic tyrosine kinase domain. The extracellular portion of the protein interacts with fibroblast growth factors, setting in motion a cascade of downstream signals, ultimately influencing mitogenesis and differentiation. A marked difference between this gene product and the other family members is its lack of a cytoplasmic tyrosine kinase domain. The result is a transmembrane receptor that could interact with other family members and potentially inhibit signaling. Multiple alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]

FGFRL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 4-1012545-G-A is Benign according to our data. Variant chr4-1012545-G-A is described in ClinVar as [Benign]. Clinvar id is 1169548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFRL1	NM_001004356.3 linkuse as main transcript	c.60G>A	p.Pro20=	synonymous_variant	2/7	ENST00000510644.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFRL1	ENST00000510644.6 linkuse as main transcript	c.60G>A	p.Pro20=	synonymous_variant	2/7	1	NM_001004356.3	P1

Frequencies

GnomAD3 genomes

AF:

0.526

AC:

79868

AN:

151962

Hom.:

21979

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.548

Gnomad AMR

AF:

0.446

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.464

Gnomad SAS

AF:

0.357

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.471

Gnomad OTH

AF:

0.528

GnomAD3 exomes

AF:

0.461

AC:

49662

AN:

107680

Hom.:

11588

AF XY:

0.452

AC XY:

27479

AN XY:

60840

show subpopulations

Gnomad AFR exome

AF:

0.740

Gnomad AMR exome

AF:

0.413

Gnomad ASJ exome

AF:

0.437

Gnomad EAS exome

AF:

0.521

Gnomad SAS exome

AF:

0.371

Gnomad FIN exome

AF:

0.457

Gnomad NFE exome

AF:

0.499

Gnomad OTH exome

AF:

0.495

GnomAD4 exome

AF:

0.468

AC:

623409

AN:

1333354

Hom.:

147372

Cov.:

AF XY:

0.464

AC XY:

306066

AN XY:

660330

show subpopulations

Gnomad4 AFR exome

AF:

0.718

Gnomad4 AMR exome

AF:

0.412

Gnomad4 ASJ exome

AF:

0.432

Gnomad4 EAS exome

AF:

0.402

Gnomad4 SAS exome

AF:

0.366

Gnomad4 FIN exome

AF:

0.458

Gnomad4 NFE exome

AF:

0.473

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.526

AC:

79965

AN:

152074

Hom.:

22012

Cov.:

AF XY:

0.518

AC XY:

38470

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.700

Gnomad4 AMR

AF:

0.446

Gnomad4 ASJ

AF:

0.439

Gnomad4 EAS

AF:

0.464

Gnomad4 SAS

AF:

0.359

Gnomad4 FIN

AF:

0.439

Gnomad4 NFE

AF:

0.471

Gnomad4 OTH

AF:

0.530

Alfa

AF:

0.483

Hom.:

3199

Bravo

AF:

0.537

Asia WGS

AF:

0.454

AC:

1576

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

FGFRL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.8

DANN

Benign

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

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