rs4647932

Positions:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001004356.3(FGFRL1):c.1391C>A(p.Pro464Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000237 in 1,609,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P464A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00044 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

FGFRL1
NM_001004356.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.63

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0040918887).

BP6

Variant 4-1025223-C-A is Benign according to our data. Variant chr4-1025223-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1583917.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFRL1	NM_001004356.3 linkuse as main transcript	c.1391C>A	p.Pro464Gln	missense_variant	7/7	ENST00000510644.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FGFRL1	ENST00000510644.6 linkuse as main transcript	c.1391C>A	p.Pro464Gln	missense_variant	7/7	1	NM_001004356.3	P1
FGFRL1	ENST00000264748.6 linkuse as main transcript	c.1391C>A	p.Pro464Gln	missense_variant	6/6	1		P1
FGFRL1	ENST00000504138.5 linkuse as main transcript	c.1391C>A	p.Pro464Gln	missense_variant	7/7	1		P1
FGFRL1	ENST00000398484.6 linkuse as main transcript	c.1391C>A	p.Pro464Gln	missense_variant	8/8	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000440

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000488

AC:

115

AN:

235606

Hom.:

AF XY:

0.000449

AC XY:

AN XY:

129232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00466

Gnomad NFE exome

AF:

0.000134

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.000216

AC:

315

AN:

1456996

Hom.:

Cov.:

AF XY:

0.000211

AC XY:

153

AN XY:

724506

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00429

Gnomad4 NFE exome

AF:

0.0000757

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000440

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000673

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000176

Hom.:

655

ExAC

AF:

0.000298

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.12

T;T;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.52

.;.;.;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.0041

T;T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.9

L;L;L;L

MutationTaster

Benign

0.65

D;D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.86

N;N;N;N

REVEL

Benign

0.064

Sift

Benign

0.067

T;T;T;T

Sift4G

Uncertain

0.0050

D;D;D;D

Polyphen

0.0060

B;B;B;B

Vest4

0.13

MVP

0.39

MPC

0.14

ClinPred

0.032

GERP RS

1.5

Varity_R

0.025

gMVP

0.20

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