Variant rs4647944 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001004356.3(FGFRL1):c.1072+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 1,523,476 control chromosomes in the GnomAD database, including 2,988 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.048 ( 229 hom., cov: 33)

Exomes 𝑓: 0.061 ( 2759 hom. )

Consequence

FGFRL1
NM_001004356.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.94

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 made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0628 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.1072+47G>A		intron_variant		ENST00000510644.6	NP_001004356.1	Q8N441A0PJ49

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FGFRL1	ENST00000510644.6 linkuse as main transcript	c.1072+47G>A	intron_variant	1	NM_001004356.3	ENSP00000425025.1	Q8N441
FGFRL1	ENST00000264748.6 linkuse as main transcript	c.1072+47G>A	intron_variant	1		ENSP00000264748.6	Q8N441
FGFRL1	ENST00000504138.5 linkuse as main transcript	c.1072+47G>A	intron_variant	1		ENSP00000423091.1	Q8N441
FGFRL1	ENST00000398484.6 linkuse as main transcript	c.1072+47G>A	intron_variant	5		ENSP00000381498.2	Q8N441

Frequencies

GnomAD3 genomes

AF:

0.0484

AC:

7361

AN:

151968

Hom.:

229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0165

Gnomad AMI

AF:

0.0395

Gnomad AMR

AF:

0.0657

Gnomad ASJ

AF:

0.125

Gnomad EAS

AF:

0.0197

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.0356

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0643

Gnomad OTH

AF:

0.0744

GnomAD3 exomes

AF:

0.0563

AC:

9837

AN:

174738

Hom.:

337

AF XY:

0.0569

AC XY:

5478

AN XY:

96328

show subpopulations

Gnomad AFR exome

AF:

0.0154

Gnomad AMR exome

AF:

0.0640

Gnomad ASJ exome

AF:

0.135

Gnomad EAS exome

AF:

0.0195

Gnomad SAS exome

AF:

0.0315

Gnomad FIN exome

AF:

0.0374

Gnomad NFE exome

AF:

0.0695

Gnomad OTH exome

AF:

0.0738

GnomAD4 exome

AF:

0.0611

AC:

83815

AN:

1371392

Hom.:

2759

Cov.:

AF XY:

0.0607

AC XY:

40987

AN XY:

675748

show subpopulations

Gnomad4 AFR exome

AF:

0.0173

Gnomad4 AMR exome

AF:

0.0638

Gnomad4 ASJ exome

AF:

0.129

Gnomad4 EAS exome

AF:

0.0261

Gnomad4 SAS exome

AF:

0.0300

Gnomad4 FIN exome

AF:

0.0354

Gnomad4 NFE exome

AF:

0.0648

Gnomad4 OTH exome

AF:

0.0639

GnomAD4 genome

AF:

0.0484

AC:

7362

AN:

152084

Hom.:

229

Cov.:

AF XY:

0.0468

AC XY:

3480

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.0165

Gnomad4 AMR

AF:

0.0658

Gnomad4 ASJ

AF:

0.125

Gnomad4 EAS

AF:

0.0196

Gnomad4 SAS

AF:

0.0295

Gnomad4 FIN

AF:

0.0356

Gnomad4 NFE

AF:

0.0644

Gnomad4 OTH

AF:

0.0750

Alfa

AF:

0.0652

Hom.:

Bravo

AF:

0.0496

Asia WGS

AF:

0.0480

AC:

166

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.11

DANN

Benign

0.88

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over