rs4647940

chr4-1026603-C-Gchr4-1026603-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001004356.3(FGFRL1):c.*1256C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 259,074 control chromosomes in the GnomAD database, including 2,637 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 0.13 (1293 hom., cov: 34)
  • Exomes 𝑓: 0.15 (1344 hom.)
• Consequence: FGFRL1 NM_001004356.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGFRL1	NM_001004356.3	c.*1256C>G		3_prime_UTR_variant	7/7	ENST00000510644.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGFRL1	ENST00000510644.6	c.*1256C>G		3_prime_UTR_variant	7/7	1	NM_001004356.3	P1
FGFRL1	ENST00000264748.6	c.*1256C>G		3_prime_UTR_variant	6/6	1		P1
FGFRL1	ENST00000398484.6	c.*1256C>G		3_prime_UTR_variant	8/8	5		P1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19092 AN: 152138 Hom.: 1294 Cov.: 34

Gnomad AFR AF: 0.0785

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.150 AC: 16055 AN: 106818 Hom.: 1344 Cov.: 0 AF XY: 0.156 AC XY: 9165 AN XY: 58730

Gnomad4 AFR exome AF: 0.0775

Gnomad4 AMR exome AF: 0.0739

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.149

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.137

GnomAD4 genome AF: 0.125 AC: 19086 AN: 152256 Hom.: 1293 Cov.: 34 AF XY: 0.126 AC XY: 9373 AN XY: 74448

Gnomad4 AFR AF: 0.0784

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.139

Alfa AF: 0.0560 Hom.: 64

Bravo AF: 0.120

Asia WGS AF: 0.161 AC: 565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	5.1
Dann	Benign	0.71

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

Other links and lift over

dbSNP: rs4647940; hg19: chr4-1020391;