chr4-1022236-G-A

Position:

chr4-1022236-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001004356.3(FGFRL1):c.113G>A(p.Arg38Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000323 in 1,554,480 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R38R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00016 ( 1 hom., cov: 34)

Exomes 𝑓: 0.00034 ( 7 hom. )

Consequence

FGFRL1
NM_001004356.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.02

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009086192).

BP6

Variant 4-1022236-G-A is Benign according to our data. Variant chr4-1022236-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2421658.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFRL1	NM_001004356.3 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant	3/7	ENST00000510644.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFRL1	ENST00000510644.6 linkuse as main transcript	c.113G>A	p.Arg38Gln	missense_variant	3/7	1	NM_001004356.3	P1

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152118

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:

0.00498

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000699

AC:

134

AN:

191774

Hom.:

AF XY:

0.000878

AC XY:

AN XY:

105890

show subpopulations

Gnomad AFR exome

AF:

0.0000866

Gnomad AMR exome

AF:

0.0000734

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00534

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00108

GnomAD4 exome

AF:

0.000340

AC:

477

AN:

1402246

Hom.:

Cov.:

AF XY:

0.000482

AC XY:

333

AN XY:

690544

show subpopulations

Gnomad4 AFR exome

AF:

0.0000316

Gnomad4 AMR exome

AF:

0.0000517

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00556

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000556

Gnomad4 OTH exome

AF:

0.000417

GnomAD4 genome

AF:

0.000164

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74446

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:

0.00519

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000139

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.000721

AC:

Asia WGS

AF:

0.00375

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Apr 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

T;T;T;.;.;T

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.85

.;.;.;T;D;D

MetaRNN

Benign

0.0091

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.42

N;N;N;.;.;N

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.1

N;N;N;N;N;N

REVEL

Benign

0.061

Sift

Benign

0.30

T;T;T;T;D;T

Sift4G

Benign

0.24

T;T;T;D;T;T

Polyphen

0.22

B;B;B;.;.;B

Vest4

0.42

MutPred

0.43

Loss of MoRF binding (P = 0.0382);Loss of MoRF binding (P = 0.0382);Loss of MoRF binding (P = 0.0382);Loss of MoRF binding (P = 0.0382);Loss of MoRF binding (P = 0.0382);Loss of MoRF binding (P = 0.0382);

MVP

0.45

MPC

0.27

ClinPred

0.058

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.073

gMVP

0.65

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