4-1026603-C-T

Variant names:

• chr4-1026603-C-T
• rs4647940
• NM_001004356.3:c.*1256C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001004356.3(FGFRL1):​c.*1256C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000934 in 107,052 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: FGFRL1 NM_001004356.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.332
• Publications: 12 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGFRL1	NM_001004356.3	c.*1256C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000510644.6	NP_001004356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFRL1	ENST00000510644.6	c.*1256C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001004356.3	ENSP00000425025.1
FGFRL1	ENST00000264748.6	c.*1256C>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000264748.6
FGFRL1	ENST00000398484.6	c.*1256C>T		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000381498.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000934 AC: 1 AN: 107052 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 58850

African (AFR) AF: 0.00 AC: 0 AN: 1896

American (AMR) AF: 0.00 AC: 0 AN: 2874

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2702

East Asian (EAS) AF: 0.00 AC: 0 AN: 2278

South Asian (SAS) AF: 0.00 AC: 0 AN: 20718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5994

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 392

European-Non Finnish (NFE) AF: 0.0000154 AC: 1 AN: 64746

Other (OTH) AF: 0.00 AC: 0 AN: 5452

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 64

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.6
DANN	Benign	0.62
PhyloP100		0.33

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

Other links and lift over

dbSNP: rs4647940; hg19: chr4-1020391;