Variant 4-1023731-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004356.3(FGFRL1):c.433+10G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,558,602 control chromosomes in the GnomAD database, including 1,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 134 hom., cov: 31)

Exomes 𝑓: 0.041 ( 1406 hom. )

Consequence

FGFRL1
NM_001004356.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.406

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-1023731-G-C is Benign according to our data. Variant chr4-1023731-G-C is described in ClinVar as [Benign]. Clinvar id is 1170809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGFRL1	NM_001004356.3 linkuse as main transcript	c.433+10G>C		intron_variant		ENST00000510644.6	NP_001004356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGFRL1	ENST00000510644.6 linkuse as main transcript	c.433+10G>C		intron_variant		1	NM_001004356.3	ENSP00000425025	P1

Frequencies

GnomAD3 genomes

AF:

0.0342

AC:

5197

AN:

152034

Hom.:

132

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0342

Gnomad ASJ

AF:

0.0466

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0476

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0391

Gnomad OTH

AF:

0.0531

GnomAD3 exomes

AF:

0.0478

AC:

7735

AN:

161912

Hom.:

258

AF XY:

0.0466

AC XY:

4090

AN XY:

87804

show subpopulations

Gnomad AFR exome

AF:

0.0143

Gnomad AMR exome

AF:

0.0231

Gnomad ASJ exome

AF:

0.0490

Gnomad EAS exome

AF:

0.136

Gnomad SAS exome

AF:

0.0157

Gnomad FIN exome

AF:

0.0570

Gnomad NFE exome

AF:

0.0522

Gnomad OTH exome

AF:

0.0462

GnomAD4 exome

AF:

0.0407

AC:

57263

AN:

1406452

Hom.:

1406

Cov.:

AF XY:

0.0402

AC XY:

27914

AN XY:

694356

show subpopulations

Gnomad4 AFR exome

AF:

0.0113

Gnomad4 AMR exome

AF:

0.0232

Gnomad4 ASJ exome

AF:

0.0408

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.0141

Gnomad4 FIN exome

AF:

0.0544

Gnomad4 NFE exome

AF:

0.0408

Gnomad4 OTH exome

AF:

0.0443

GnomAD4 genome

AF:

0.0343

AC:

5212

AN:

152150

Hom.:

134

Cov.:

AF XY:

0.0344

AC XY:

2556

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0129

Gnomad4 AMR

AF:

0.0342

Gnomad4 ASJ

AF:

0.0466

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.0174

Gnomad4 FIN

AF:

0.0476

Gnomad4 NFE

AF:

0.0391

Gnomad4 OTH

AF:

0.0578

Alfa

AF:

0.0341

Hom.:

Bravo

AF:

0.0338

Asia WGS

AF:

0.0810

AC:

282

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

FGFRL1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 23, 2019

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

-0.81

CADD

Benign

7.7

DANN

Benign

0.79

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