NM_001004356.3:c.22C>A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004356.3(FGFRL1):c.22C>A(p.Leu8Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000213 in 1,409,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L8L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

FGFRL1
NM_001004356.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.828

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11433971).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004356.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGFRL1	NM_001004356.3	MANE Select	c.22C>A	p.Leu8Met	missense	Exon 2 of 7	NP_001004356.1	Q8N441
FGFRL1	NM_001004358.1		c.22C>A	p.Leu8Met	missense	Exon 2 of 7	NP_001004358.1	Q8N441
FGFRL1	NM_001370296.1		c.22C>A	p.Leu8Met	missense	Exon 2 of 7	NP_001357225.1	Q8N441

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FGFRL1	ENST00000510644.6	TSL:1 MANE Select	c.22C>A	p.Leu8Met	missense	Exon 2 of 7	ENSP00000425025.1	Q8N441
FGFRL1	ENST00000264748.6	TSL:1	c.22C>A	p.Leu8Met	missense	Exon 1 of 6	ENSP00000264748.6	Q8N441
FGFRL1	ENST00000504138.5	TSL:1	c.22C>A	p.Leu8Met	missense	Exon 2 of 7	ENSP00000423091.1	Q8N441

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1409368

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

700222

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29444

American (AMR)

AF:

0.00

AC:

AN:

40122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24710

East Asian (EAS)

AF:

0.00

AC:

AN:

33904

South Asian (SAS)

AF:

0.00

AC:

AN:

81182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

44570

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1091574

Other (OTH)

AF:

0.0000172

AC:

AN:

58198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.16

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.28

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.90

PhyloP100

-0.83

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

0.010

REVEL

Benign

0.13

Sift

Benign

0.24

Sift4G

Benign

0.19

Polyphen

0.093

Vest4

0.35

MutPred

0.41

Loss of glycosylation at P5 (P = 0.0222)

MVP

0.62

MPC

0.14

ClinPred

0.22

GERP RS

-3.9

PromoterAI

-0.13

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.066

gMVP

0.29

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over