rs4647942

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004356.3(FGFRL1):c.60G>A(p.Pro20Pro) 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

Publications

9 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FGFRL1	NM_001004356.3 link	c.60G>A	p.Pro20Pro	synonymous_variant	Exon 2 of 7	ENST00000510644.6	NP_001004356.1	Q8N441A0PJ49

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFRL1	ENST00000510644.6 link	c.60G>A	p.Pro20Pro	synonymous_variant	Exon 2 of 7	1	NM_001004356.3	ENSP00000425025.1		Q8N441

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

GnomAD2 exomes

AF:

0.461

AC:

49662

AN:

107680

AF XY:

0.452

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 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

African (AFR)

AF:

0.718

AC:

19650

AN:

27374

American (AMR)

AF:

0.412

AC:

13138

AN:

31860

Ashkenazi Jewish (ASJ)

AF:

0.432

AC:

10254

AN:

23726

East Asian (EAS)

AF:

0.402

AC:

12128

AN:

30134

South Asian (SAS)

AF:

0.366

AC:

27774

AN:

75808

European-Finnish (FIN)

AF:

0.458

AC:

17352

AN:

37890

Middle Eastern (MID)

AF:

0.442

AC:

2429

AN:

5498

European-Non Finnish (NFE)

AF:

0.473

AC:

494474

AN:

1045616

Other (OTH)

AF:

0.473

AC:

26210

AN:

55448

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

16737

33473

50210

66946

83683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14866

29732

44598

59464

74330

<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

AF:

0.526

AC:

79965

AN:

152074

Hom.:

22012

Cov.:

AF XY:

0.518

AC XY:

38470

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.700

AC:

29083

AN:

41520

American (AMR)

AF:

0.446

AC:

6819

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1522

AN:

3470

East Asian (EAS)

AF:

0.464

AC:

2385

AN:

5136

South Asian (SAS)

AF:

0.359

AC:

1732

AN:

4830

European-Finnish (FIN)

AF:

0.439

AC:

4656

AN:

10596

Middle Eastern (MID)

AF:

0.555

AC:

162

AN:

292

European-Non Finnish (NFE)

AF:

0.471

AC:

31993

AN:

67930

Other (OTH)

AF:

0.530

AC:

1119

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1975

3950

5924

7899

9874

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

FGFRL1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

(source)

DANN

Benign

0.97

PhyloP100

-1.8

PromoterAI

0.0084

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over