rs4647944

Variant names:

• chr4-1024711-G-A
• rs4647944
• NM_001004356.3:c.1072+47G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-1024711-G-A
• chr4-1024711-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 2 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
FGFRL1	NM_001004356.3	c.1072+47G>A		intron_variant	Intron 6 of 6	ENST00000510644.6	NP_001004356.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGFRL1	ENST00000510644.6	c.1072+47G>A		intron_variant	Intron 6 of 6	1	NM_001004356.3	ENSP00000425025.1
FGFRL1	ENST00000264748.6	c.1072+47G>A		intron_variant	Intron 5 of 5	1		ENSP00000264748.6
FGFRL1	ENST00000504138.5	c.1072+47G>A		intron_variant	Intron 6 of 6	1		ENSP00000423091.1
FGFRL1	ENST00000398484.6	c.1072+47G>A		intron_variant	Intron 7 of 7	5		ENSP00000381498.2

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7361 AN: 151968 Hom.: 229 Cov.: 33

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

GnomAD2 exomes AF: 0.0563 AC: 9837 AN: 174738 AF XY: 0.0569

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 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.: 29 AF XY: 0.0607 AC XY: 40987 AN XY: 675748

African (AFR) AF: 0.0173 AC: 546 AN: 31636

American (AMR) AF: 0.0638 AC: 2430 AN: 38082

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 2858 AN: 22218

East Asian (EAS) AF: 0.0261 AC: 1008 AN: 38664

South Asian (SAS) AF: 0.0300 AC: 2288 AN: 76214

European-Finnish (FIN) AF: 0.0354 AC: 1360 AN: 38430

Middle Eastern (MID) AF: 0.134 AC: 727 AN: 5440

European-Non Finnish (NFE) AF: 0.0648 AC: 68958 AN: 1063746

Other (OTH) AF: 0.0639 AC: 3640 AN: 56962

GnomAD4 genome AF: 0.0484 AC: 7362 AN: 152084 Hom.: 229 Cov.: 33 AF XY: 0.0468 AC XY: 3480 AN XY: 74354

African (AFR) AF: 0.0165 AC: 684 AN: 41492

American (AMR) AF: 0.0658 AC: 1007 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 435 AN: 3470

East Asian (EAS) AF: 0.0196 AC: 101 AN: 5158

South Asian (SAS) AF: 0.0295 AC: 142 AN: 4820

European-Finnish (FIN) AF: 0.0356 AC: 377 AN: 10600

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0644 AC: 4373 AN: 67936

Other (OTH) AF: 0.0750 AC: 158 AN: 2106

Alfa AF: 0.0652 Hom.: 73

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
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs4647944; hg19: chr4-1018499; COSMIC: COSV53259079; COSMIC: COSV53259079;