rs4647930

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001004356.3(FGFRL1):c.1085C>A(p.Pro362Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 1,591,946 control chromosomes in the GnomAD database, including 53,995 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.19 ( 3520 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50475 hom. )

Consequence

FGFRL1
NM_001004356.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.28

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015857816).

BP6

Variant 4-1024917-C-A is Benign according to our data. Variant chr4-1024917-C-A is described in ClinVar as [Benign]. Clinvar id is 1164138.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 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.1085C>A	p.Pro362Gln	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.1085C>A	p.Pro362Gln	missense_variant	7/7	1	NM_001004356.3	P1
FGFRL1	ENST00000264748.6 linkuse as main transcript	c.1085C>A	p.Pro362Gln	missense_variant	6/6	1		P1
FGFRL1	ENST00000504138.5 linkuse as main transcript	c.1085C>A	p.Pro362Gln	missense_variant	7/7	1		P1
FGFRL1	ENST00000398484.6 linkuse as main transcript	c.1085C>A	p.Pro362Gln	missense_variant	8/8	5		P1

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29382

AN:

152000

Hom.:

3523

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.177

Gnomad ASJ

AF:

0.358

Gnomad EAS

AF:

0.0814

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.232

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.216

GnomAD3 exomes

AF:

0.220

AC:

51836

AN:

235146

Hom.:

6500

AF XY:

0.228

AC XY:

29480

AN XY:

129234

show subpopulations

Gnomad AFR exome

AF:

0.0622

Gnomad AMR exome

AF:

0.138

Gnomad ASJ exome

AF:

0.360

Gnomad EAS exome

AF:

0.0836

Gnomad SAS exome

AF:

0.220

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.275

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.258

AC:

371823

AN:

1439828

Hom.:

50475

Cov.:

AF XY:

0.258

AC XY:

184817

AN XY:

715000

show subpopulations

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.361

Gnomad4 EAS exome

AF:

0.0879

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.232

Gnomad4 NFE exome

AF:

0.276

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.193

AC:

29379

AN:

152118

Hom.:

3520

Cov.:

AF XY:

0.192

AC XY:

14257

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0629

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.358

Gnomad4 EAS

AF:

0.0812

Gnomad4 SAS

AF:

0.203

Gnomad4 FIN

AF:

0.232

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.243

Hom.:

5012

Bravo

AF:

0.182

TwinsUK

AF:

0.281

AC:

1043

ALSPAC

AF:

0.278

AC:

1072

ESP6500AA

AF:

0.0742

AC:

326

ESP6500EA

AF:

0.270

AC:

2315

ExAC

AF:

0.220

AC:

26631

Asia WGS

AF:

0.179

AC:

622

AN:

3476

EpiCase

AF:

0.272

EpiControl

AF:

0.276

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.29

Cadd

Benign

Dann

Benign

0.97

DEOGEN2

Benign

0.18

T;T;T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.97

MetaRNN

Benign

0.0016

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;L;L

MutationTaster

Benign

8.5e-8

P;P;P;P

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-2.0

N;N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.10

B;B;B;B

Vest4

0.19

MPC

0.16

ClinPred

0.010

GERP RS

3.9

Varity_R

0.073

gMVP

0.46

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