4-1012577-G-A

Variant names:

• chr4-1012577-G-A
• rs1715655800
• NM_001004356.3:c.79+13G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001004356.3(FGFRL1):​c.79+13G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 35)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FGFRL1 NM_001004356.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001004356.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFRL1	NM_001004356.3	MANE Select	c.79+13G>A		intron	N/A	NP_001004356.1	Q8N441
	FGFRL1	NM_001004358.1		c.79+13G>A		intron	N/A	NP_001004358.1	Q8N441
	FGFRL1	NM_001370296.1		c.79+13G>A		intron	N/A	NP_001357225.1	Q8N441

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGFRL1	ENST00000510644.6	TSL:1 MANE Select	c.79+13G>A		intron	N/A	ENSP00000425025.1	Q8N441
	FGFRL1	ENST00000264748.6	TSL:1	c.79+13G>A		intron	N/A	ENSP00000264748.6	Q8N441
	FGFRL1	ENST00000504138.5	TSL:1	c.79+13G>A		intron	N/A	ENSP00000423091.1	Q8N441

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.81e-7 AC: 1 AN: 1135072 Hom.: 0 Cov.: 15 AF XY: 0.00000177 AC XY: 1 AN XY: 565714

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23042

American (AMR) AF: 0.0000441 AC: 1 AN: 22670

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20250

East Asian (EAS) AF: 0.00 AC: 0 AN: 27782

South Asian (SAS) AF: 0.00 AC: 0 AN: 64892

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 889602

Other (OTH) AF: 0.00 AC: 0 AN: 48638

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 35

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		-0.31
PromoterAI		-0.028	Neutral

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: rs1715655800; hg19: chr4-1006365;